Omega-conopeptides

ABSTRACT

The invention relates to ω-conopeptides, derivatives or pharmaceutically acceptable salts thereof, and uses thereof, including the treatment of neurologic and psychiatric disorders, such as anticonvulsant agents, as neuroprotective agents, as cardiovascular agents or for the management of pain. The invention further relates to nucleic acid sequences encoding the conopeptides and encoding propeptides, as well as the propeptides.

CROSS REFERENCE TO RELATED APPLICATIONS

[0001] The present application claims benefit under 35 USC §119(e) toU.S. provisional patent applications Ser. No. 60/219,616 filed on Jul.21, 2000 and Ser. No. 60/265,888 filed on Feb. 5, 2001. Each of theseapplications are incorporated herein by reference.

[0002] This invention was made with Government support under Grant No.PO1 GM48677 awarded by the National Institute of General MedicalSciences, National Institutes of Health, Bethesda, Md. The United StatesGovernment has certain rights in the invention.

BACKGROUND OF THE INVENTION

[0003] The invention relates to ω-conopeptides, derivatives orpharmaceutically acceptable salts thereof, and uses thereof, includingthe treatment of neurologic and psychiatric disorders, such asanticonvulsant agents, as neuroprotective agents, as cardiovascularagents or for the management of pain. The invention further relates tonucleic acid sequences encoding the conopeptides and encodingpropeptides, as well as the propeptides.

[0004] The publications and other materials used herein to illuminatethe background of the invention, and in particular, cases to provideadditional details respecting the practice, are incorporated byreference, and for convenience are referenced in the following text byauthor and date and are listed alphabetically by author in the appendedbibliography.

[0005] Conus is a genus of predatory marine gastropods (snails) whichenvenomate their prey. Venomous cone snails use a highly developedprojectile apparatus to deliver their cocktail of toxic conotoxins intotheir prey. In fish-eating species such as Conus magus the cone detectsthe presence of the fish using chemosensors in its siphon and when closeenough extends its proboscis and fires a hollow harpoon-like toothcontaining venom into the fish. This immobilizes the fish and enablesthe cone snail to wind it into its mouth via an attached filament.

[0006] For general information on Conus and their venom see the websiteaddress http://grimwade.biochem.unimelb.edu.au/cone/referenc.html. Preycapture is accomplished through a sophisticated arsenal of peptideswhich target specific ion channel and receptor subtypes. Each Conusspecies venom appears to contain a unique set of 50-200 peptides. Thecomposition of the venom differs greatly between species and betweenindividual snails within each species, each optimally evolved toparalyse it's prey. The active components of the venom are smallpeptides toxins, typically 12-30 amino acid residues in length and aretypically highly constrained peptides due to their high density ofdisulphide bonds.

[0007] The venoms consist of a large number of different peptidecomponents that when separated exhibit a range of biological activities:when injected into mice they elicit a range of physiological responsesfrom shaking to depression. The paralytic components of the venom thathave been the focus of recent investigation are the α-, ω- andμ-conotoxins. All of these conotoxins act by preventing neuronalcommunication, but each targets a different aspect of the process toachieve this. The α-conotoxins target nicotinic ligand gated channels,the μ-conotoxins target the voltage-gated sodium channels and theω-conotoxins target the voltage-gated calcium channels (Olivera et al.,1985; Olivera et al., 1990). For example a linkage has been establishedbetween α-, αA- &Φ-conotoxins and the nicotinic ligand-gated ionchannel; ω-conotoxins and the voltage-gated calcium channel;μ-conotoxins and the voltage-gated sodium channel; δ-conotoxins and thevoltage-gated sodium channel; κ-conotoxins and the voltage-gatedpotassium channel; conantokins and the ligand-gated glutamate (NMDA)channel.

[0008] However, the structure and function of only a small minority ofthese peptides have been determined to date. For peptides where functionhas been determined, three classes of targets have been elucidated:voltage-gated ion channels; ligand-gated ion channels, andG-protein-linked receptors.

[0009] Conus peptides which target voltage-gated ion channels includethose that delay the inactivation of sodium channels, as well asblockers specific for sodium channels, calcium channels and potassiumchannels. Peptides that target ligand-gated ion channels includeantagonists of NMDA and serotonin receptors, as well as competitive andnoncompetitive nicotinic receptor antagonists. Peptides which act onG-protein receptors include neurotensin and vasopressin receptoragonists. The unprecedented pharmaceutical selectivity of conotoxins isat least in part defined by a specific disulfide bond frameworkscombined with hypervariable amino acids within disulfide loops (for areview see McIntosh et al., 1998).

[0010] There are drugs used in the treatment of pain, which are known inthe literature and to the skilled artisan. See, for example, MerckManual, 16th Ed. (1992). However, there is a demand for more activeanalgesic agents with diminished side effects and toxicity and which arenon-addictive. The ideal analgesic would reduce the awareness of pain,produce analgesia over a wide range of pain types, act satisfactorilywhether given orally or parenterally, produce minimal or no sideeffects, be free from tendency to produce tolerance and drug dependence.

[0011] Due to the high potency and exquisite selectivity of theconopeptides, several are in various stages of clinical development fortreatment of human disorders. For example, two Conus peptides are beingdeveloped for the treatment of pain. The most advanced is ω-conotoxinMVIIA (ziconotide), an N-type calcium channel blocker (see Heading, C.,1999;

[0012] U.S. Pat. No. 5,859,186). ω-Conotoxin MVIIA, isolated from Conusmagus, is approximately 1000 times more potent than morphine, yet doesnot produce the tolerance or addictive properties of opiates.ω-Conotoxin MVIIA has completed Phase III (final stages) of humanclinical trials and has been approved as a therapeutic agent.ω-Conotoxin MVIIA is introduced into human patients by means of animplantable, programmable pump with a catheter threaded into theintrathecal space. Preclinical testing for use in post-surgical pain isbeing carried out on another Conus peptide, contulakin-G, isolated fromConus geographus (Craig et al. 1999).

[0013] Contulakin-G is a 16 amino acid O-linked glycopeptide whoseC-terminus resembles neurotensin. It is an agonist of neurotensinreceptors, but appears significantly more potent than neurotensin ininhibiting pain in in vivo assays.

[0014] Ischemic damage to the central nervous system (CNS) may resultform either global or focal ischemic conditions. Global ischemia occursunder conditions in which blood flow to the entire brain ceases for aperiod of time, such as may result from cardiac arrest. Focal ischemiaoccurs under conditions in which a portion of the brain is deprived ofits normal blood supply, such as may result from thromboembolyticocclusion of a cerebral vessel, traumatic head or spinal cord injury,edema or brain or spinal cord tumors. Both global and focal ischemicconditions have the potential for widespread neuronal damage, even ifthe global ischemic condition is transient or the focal conditionaffects a very limited area.

[0015] Epilepsy is a recurrent paroxysmal disorder of cerebral functioncharacterized by sudden brief attacks of altered consciousness, motoractivity, sensory phenomena or inappropriate behavior caused by abnormalexcessive discharge of cerebral neurons. Convulsive seizures, the mostcommon form of attacks, begin with loss of consciousness and motorcontrol, and tonic or clonic jerking of all extremities but anyrecurrent seizure pattern may be termed epilepsy. The term primary oridiopathic epilepsy denotes those cases where no cause for the seizurescan be identified. Secondary or symptomatic epilepsy designates thedisorder when it is associated with such factors as trauma, neoplasm,infection, developmental abnormalities, cerebrovascular disease, orvarious metabolic conditions. Epileptic seizures are classified aspartial seizures (focal, local seizures) or generalized seizures(convulsive or nonconvulsive). Classes of partial seizures includesimple partial seizures, complex partial seizures and partial seizuressecondarily generalized. Classes of generalized seizures include absenceseizures, atypical absence seizures, myoclonic seizures, clonicseizures, tonic seizures, tonic-clonic seizures (grand mal) and atonicseizures. Therapeutics having anticonvulsant properties are used in thetreatment of seizures. Most therapeutics used to abolish or attenuateseizures act at least through effects that reduce the spread ofexcitation from seizure foci and prevent detonation and disruption offunction of normal aggregates of neurons. Traditional anticonvulsantsthat have been utilized include phenytoin, phenobarbital, primidone,carbamazepine, ethosuximide, clonazepam and valproate. Several novel andchemically diverse anticonvulsant medications recently have beenapproved for marketing, including lamotrigine, ferlbamate, gabapentinand topiramate. For further details of seizures and their therapy, seeRall & Schleifer (1985) and The Merck Manual (1992).

[0016] In view of a large number of biologically active substances inConus species it is desirable to further characterize them and toidentify peptides capable of treating disorders involving voltage gatedion channels, such as stroke and pain. Surprisingly, and in accordancewith this invention, Applicants have discovered novel conotoxins thatcan be useful for the treatment of disorders involving voltage gated ionchannels and could address a long felt need for a safe and effectivetreatment.

SUMMARY OF THE INVENTION

[0017] The present invention is directed to ω-conopeptides, derivativesor pharmaceutically acceptable salts thereof, and uses thereof,including the treatment of neurologic and psychiatric disorders, such asanticonvulsant agents, as neuroprotective agents, as cardiovascularagents or for the management of pain. The invention is further directedto nucleic acid sequences encoding the ω-conopeptides and encodingpropeptides, as well as the propeptides.

[0018] More specifically, the present invention is directed toω-conopeptides, having the amino acid sequences set forth in Table 2below.

[0019] The present invention is also directed to derivatives orpharmaceutically acceptable salts of the ω-conopeptides or thederivatives. Examples of derivatives include peptides in which the Argresidues may be substituted by Lys, ornithine, homoargine, nor-Lys,N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys or any syntheticbasic amino acid; the Lys residues may be substituted by Arg, ornithine,homoargine, nor-Lys, or any synthetic basic amino acid; the Tyr residuesmay be substituted with meta-Tyr, ortho-Tyr, nor-Tyr, mono-halo-Tyr,di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr, nitro-Tyr or any synthetichydroxy containing amino acid; the Ser residues may be substituted withThr or any synthetic hydroxylated amino acid; the Thr residues may besubstituted with Ser or any synthetic hydroxylated amino acid; the Pheresidues may be substituted with any synthetic aromatic amino acid; theTrp residues may be substituted with Trp (D), neo-Trp, halo-Trp (D or L)or any aromatic synthetic amino acid; and the Asn, Ser, Thr or Hypresidues may be glycosylated. The halogen may be iodo, chloro, fluoro orbromo; preferably iodo for halogen substituted-Tyr and bromo forhalogen-substituted Trp. The Tyr residues may also be substituted withthe 3-hydroxyl or 2-hydroxyl isomers (meta-Tyr or ortho-Tyr,respectively) and corresponding O-sulpho- and O-phospho-derivatives. Theacidic amino acid residues may be substituted with any synthetic acidicamino acid, e.g., tetrazolyl derivatives of Gly and Ala. The aliphaticamino acids may be substituted by synthetic derivatives bearingnon-natural aliphatic branched or linear side chains C_(n)H_(2n+2)up toand including n=8. The Cys residues may be in D or L configuration andmay optionally be substituted with homocysteine (D or L).

[0020] Examples of synthetic aromatic amino acid include, but are notlimited to, nitro-Phe, 4-substituted-Phe wherein the substituent isC₁-C₃ alkyl, carboxyl, hyrdroxymethyl, sulphomethyl, halo, phenyl, —CHO,—CN, —SO₃H and —NHAc. Examples of synthetic hydroxy containing aminoacid, include, but are not limited to, such as 4-hydroxymethyl-Phe,4-hydroxyphenyl-Gly, 2,6-dimethyl-Tyr and 5-amino-Tyr. Examples ofsynthetic basic amino acids include, but are not limited to,N-1-(2-pyrazolinyl)-Arg, 2-(4-piperinyl)-Gly, 2-(4-piperinyl)-Ala,2-[3-(2S)pyrrolininyl)-Gly and 2-[3-(2S)pyrrolininyl)-Ala. These andother synthetic basic amino acids, synthetic hydroxy containing aminoacids or synthetic aromatic amino acids are described in Building BlockIndex, Version 3.0 (1999 Catalog, pages 4-47 for hydroxy containingamino acids and aromatic amino acids and pages 66-87 for basic aminoacids; see also http://www.amino-acids.com), incorporated herein byreference, by and available from RSP Amino Acid Analogues, Inc.,Worcester, Mass. Examples of synthetic acid amino acids include thosederivatives bearing acidic functionality, including carboxyl, phosphate,sulfonate and synthetic tetrazolyl derivatives such as described byOrnstein et al. (1993) and in U.S. Pat. No. 5,331,001, each incorporatedherein by reference.

[0021] Optionally, in the ω-conopeptides of the present invention, theAsn residues may be modified to contain an N-glycan and the Ser, Thr andHyp residues may be modified to contain an O-glycan (e.g., g—N, g—S, g—Tand g—Hyp). In accordance with the present invention, a glycan shallmean any N—, S—or O-linked mono—, di—, tri—, poly—or oligosaccharidethat can be attached to any hydroxy, amino or thiol group of natural ormodified amino acids by synthetic or enzymatic methodologies known inthe art. The monosaccharides making up the glycan can include D-allose,D-altrose, D-glucose, D-mannose, D-gulose, D-idose, D-galactose,D-talose, D-galactosamine, D-glucosamine, D-N-acetyl-glucosamine(GlcNAc), D-N-acetyl-galactosamine (GalNAc), D-fucose or D-arabinose.These saccharides may be structurally modified, e.g., with one or moreO-sulfate, O-phosphate, O-acetyl or acidic groups, such as sialic acid,including combinations thereof. The gylcan may also include similarpolyhydroxy groups, such as D-penicillamine 2,5 and halogenatedderivatives thereof or polypropylene glycol derivatives. The glycosidiclinkage is beta and 1-4 or 1-3, preferably 1-3. The linkage between theglycan and the amino acid may be alpha or beta, preferably alpha and is1−.

[0022] Core O-glycans have been described by Van de Steen et al. (1998),incorporated herein by reference. Mucin type O-linked oligosaccharidesare attached to Ser or Thr (or other hydroxylated residues of thepresent peptides) by a GalNAc residue. The monosaccharide buildingblocks and the linkage attached to this first GalNAc residue define the“core glycans,” of which eight have been identified. The type ofglycosidic linkage (orientation and connectivities) are defined for eachcore glycan. Suitable glycans and glycan analogs are described furtherin U.S. Ser. No. 09/420,797 filed Oct. 19, 1999 and in PCT ApplicationNo. PCT/US99/24380 filed Oct. 19, 1999 (PCT Published Application No. WO00/23092), each incorporated herein by reference. A preferred glycan isGal(β1-3)GalNAc(α1→).

[0023] Optionally, in the ω-conopeptides described above, pairs of Cysresidues may be replaced pairwise with isoteric lactam orester-thioether replacements, such as Ser/(Glu or Asp), Lys/(Glu or Asp)or Cys/Ala combinations. Sequential coupling by known methods (Barnay etal., 2000; Hruby et al., 1994; Bitan et al., 1997) allows replacement ofnative Cys bridges with lactam bridges. Thioether analogs may be readilysynthesized using halo-Ala residues commercially available from RSPAmino Acid Analogues.

[0024] The present invention is further directed to a method of treatingdisorders associated with voltage gated ion channel disorders in asubject comprising administering to the subject an effective amount ofthe pharmaceutical composition comprising a therapeutically effectiveamount of a ω-conopeptide described herein or a pharmaceuticallyacceptable salt or solvate thereof. The present invention is alsodirected to a pharmaceutical composition comprising a therapeuticallyeffective amount of a ω-conopeptide described herein or apharmaceutically acceptable salt or solvate thereof and apharmaceutically acceptable carrier.

[0025] More specifically, the present invention is further directed touses of these peptides or nucleic acids as described herein, includingthe treatment of neurologic disorders, such as anticonvulsant agents, asneuroprotective agents, such as for treating stroke, as cardiovascularagents or for the management of pain.

[0026] More specifically, the present invention is also directed tonucleic acids which encode conopeptides of the present invention orwhich encodes precursor peptides for these conopeptides, as well as theprecursor peptide. The nucleic acid sequences encoding the precursorpeptides of other conopeptides of the present invention are set forth inTable 1. Table 1 also sets forth the amino acid sequences of theseprecursor peptides.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

[0027] The present invention is to ω-conopeptides, derivatives orpharmaceutically acceptable salts thereof. The present invention isfurther directed to the use of this peptide, derivatives thereof andpharmaceutically acceptable salts thereof for the treatment ofneurologic disorders, such as anticonvulsant agents, as neuroprotectiveagents, such as for treating stroke, as cardiovascular agents or for themanagement of pain, e.g. as analgesic agents. The invention is furtherdirected to nucleic acid sequences encoding the ω-conopeptides andencoding propeptides, as well as the propeptides.

[0028] The present invention, in another aspect, relates to apharmaceutical composition comprising an effective amount of anω-conopeptides, a mutein thereof, an analog thereof, an active fragmentthereof or pharmaceutically acceptable salts or solvates. Such apharmaceutical composition has the capability of acting at voltage gatedion channels, and are thus useful for treating a disorder or disease ofa living animal body, including a human, which disorder or disease isresponsive to the partial or complete blockade of voltage gated ionchannels of the central nervous system comprising the step ofadministering to such a living animal body, including a human, in needthereof a therapeutically effective amount of a pharmaceuticalcomposition of the present invention.

[0029] Voltage-gated calcium channels are present in neurons, and incardiac, smooth, and skeletal muscle and other excitable cells, and areknown to play a variety of roles in membrane excitability, musclecontraction, and cellular secretion, such as in synaptic transmission(McCleskey). In neuronal cells, voltage-gated calcium channels have beenclassified by their electrophysiological as well as by their biochemical(binding) properties. Six classes of physiologically distinct calciumchannels have been identified to date, namely the T, L, N, P, Q, andR-type channels.

[0030] It is well known that an accumulation of calcium (calciumoverload) in the brain is seen after anoxia, ischemia, migraine andother hyperactivity periods of the brain, such as after epilepticconvulsions. An uncontrolled high concentration of calcium in the cellsof the central nervous system (CNS) is known to cause most of thedegenerative changes connected with the above diseases. Compounds whichcan block the calcium channels of brain cells are therefore useful inthe treatment of stroke, anoxia, ischemia, migraine, psychosis, orepilepsy, any other convulsive disorder and in the prevention of thedegenerative changes connected with the same.

[0031] Compounds blocking the so called L-type calcium channels in theCNS are useful for the treatment of the above disorders by directlyblocking the calcium uptake in the CNS.

[0032] Further, it is well known that the so called N- and P-types ofcalcium channels, as well as possibly other types of calcium channels,are involved in the regulation of neurotransmitter release. Compoundsblocking the N- and/or P-types of calcium channels indirectly and verypowerfully prevent calcium overload in the CNS after the hyperactivityperiods of the brain as described above by inhibiting the enhancedneurotransmitter release seen after such hyperactivity periods of theCNS, and especially the neurotoxic, enhanced glutamate release aftersuch hyperactivity periods of the CNS. Furthermore, blockers of the N-and/or P-types of calcium channels, as dependent upon the selectivity ofthe compound in question, inhibit the release of various otherneurotransmitters such as aspartate, GABA, glycine, dopamine, serotoninand noradrenaline.

[0033] Thus, the pharmaceutical compositions of the present inventionare useful as neuroprotectants, cardiovascular agents, anticonvulsants,analgesics or adjuvants to general anesthetics. A “neurological disorderor disease” is a disorder or disease of the nervous system including,but not limited to, global and focal ischemic and hemorrhagic stroke,head trauma, spinal cord injury, hypoxia-induced nerve cell damage as incardiac arrest or neonatal distress or epilepsy. In addition, a“neurological disorder or disease” is a disease state and condition inwhich a neuroprotectant, anticonvulsant, analgesic and/or as an adjunctin general anesthesia may be indicated, useful, recommended orprescribed.

[0034] More specifically, the present invention is directed to the useof these compounds for the treatment and alleviation of epilepsy and asa general anticonvulsant agent. The present invention is also directedto the use of these compounds for reducing neurotoxic injury associatedwith conditions of hypoxia, anoxia or ischemia which typically followsstroke, cerebrovascular accident, brain or spinal cord trauma,myocardial infarct, physical trauma, drowning, suffocation, perinatalasphyxia, or hypoglycemic events. The present invention is furtherdirected to the use of these compounds for treating pain, includingacute and chronic pain, such migraine, nociceptive and neuropathic pain.Other uses of these compounds are described in U.S. Pat. No. 5,859,186,incorporated herein by reference.

[0035] A “neuroprotectant” is a compound capable of preventing theneuronal death associated with a neurological disorder or disease. An“anticonvulsant” is a compound capable of reducing convulsions producedby conditions such as simple partial seizures, complex partial seizures,status epilepticus, and trauma-induced seizures such as occur followinghead injury, including head surgery. An “analgesic” is a compoundcapable of relieving pain by altering perception of nociceptive stimuliwithout producing anesthesia or loss of consciousness. A “musclerelaxant” is a compound that reduces muscular tension. A “adjunct ingeneral anesthesia” is a compound useful in conjunction with anestheticagents in producing the loss of ability to perceive pain associated withthe loss of consciousness.

[0036] The invention relates as well to methods useful for treatment ofneurological disorders and diseases, including, but not limited to,global and focal ischemic and hemorrhagic stroke, head trauma, spinalcord injury, hypoxia-induced nerve cell damage such as in cardiac arrestor neonatal distress, epilepsy or other convulsive disorders withoutundesirable side effects.

[0037] Thus, in one embodiment, the invention provides a method ofreducing/alleviating/ decreasing the perception of pain by a subject orfor inducing analgesia in a subject comprising administering to thesubject an effective amount of the pharmaceutical composition comprisinga therapeutically effective amount of a ω-conopeptide described hereinor a pharmaceutically acceptable salt or solvate thereof. The pain maybe acute, persistent, inflammatory or neuropathic pain.

[0038] In a second embodiment, the invention provides a method oftreating stroke, head or spinal cord trauma or injury, anoxia,hypoxia-induced nerve cell damage, ischemia, migraine, psychosis,anxiety, schizophrenia, inflammation, movement disorder, epilepsy, anyother convulsive disorder or in the prevention of the degenerativechanges connected with the same in a subject comprising administering tothe subject an effective amount of the pharmaceutical compositioncomprising a therapeutically effective amount of a ω-conopeptidedescribed herein or a pharmaceutically acceptable salt or solvatethereof.

[0039] The ω-conopeptides described herein are sufficiently small to bechemically synthesized. General chemical syntheses for preparing theforegoing ω-conotoxin peptides are described hereinafter. Various onesof the ω-conopeptides can also be obtained by isolation and purificationfrom specific Conus species using the technique described in U.S. Pat.Nos. 4,447,356 (Olivera et al., 1984); 5,514,774; 5,719,264; and5,591,821, as well as in PCT published application WO 98/03189, thedisclosures of which are incorporated herein by reference.

[0040] Although the ω-conopeptides of the present invention can beobtained by purification from cone snails, because the amounts ofω-conopeptides obtainable from individual snails are very small, thedesired substantially pure co-conopeptides are best practically obtainedin commercially valuable amounts by chemical synthesis using solid-phasestrategy. For example, the yield from a single cone snail may be about10 micrograms or less of ω-conopeptides peptide. By “substantially pure”is meant that the peptide is present in the substantial absence of otherbiological molecules of the same type; it is preferably present in anamount of at least about 85% purity and preferably at least about 95%purity. Chemical synthesis of biologically active ω-conopeptidespeptides depends of course upon correct determination of the amino acidsequence.

[0041] The ω-conopeptides can also be produced by recombinant DNAtechniques well known in the art. Such techniques are described bySambrook et al. (1989). A gene of interest (i.e., a gene that encodes asuitable ω-conopeptides) can be inserted into a cloning site of asuitable expression vector by using standard techniques. Thesetechniques are well known to those skilled in the art. The expressionvector containing the gene of interest may then be used to transfect thedesired cell line. Standard transfection techniques such as calciumphosphate co-precipitation, DEAE-dextran transfection or electroporationmay be utilized. A wide variety of host/expression vector combinationsmay be used to express a gene encoding a conotoxin peptide of interest.Such combinations are well known to a skilled artisan. The peptidesproduced in this manner are isolated, reduced if necessary, and oxidizedto form the correct disulfide bonds.

[0042] One method of forming disulfide bonds in the ω-conopeptides ofthe present invention is the air oxidation of the linear peptides forprolonged periods under cold room temperatures or at room temperature.This procedure results in the creation of a substantial amount of thebioactive, disulfide-linked peptides. The oxidized peptides arefractionated using reverse-phase high performance liquid chromatography(HPLC) or the like, to separate peptides having different linkedconfigurations. Thereafter, either by comparing these fractions with theelution of the native material or by using a simple assay, theparticular fraction having the correct linkage for maximum biologicalpotency is easily determined. However, because of the dilution resultingfrom the presence of other fractions of less biopotency, a somewhathigher dosage may be required.

[0043] The peptides are synthesized by a suitable method, such as byexclusively solid-phase techniques, by partial solid-phase techniques,by fragment condensation or by classical solution couplings.

[0044] In conventional solution phase peptide synthesis, the peptidechain can be prepared by a series of coupling reactions in whichconstituent amino acids are added to the growing peptide chain in thedesired sequence. Use of various coupling reagents, e.g.,dicyclohexylcarbodiimide or diisopropylcarbonyldimidazole, variousactive esters, e.g., esters of N-hydroxyphthalimide orN-hydroxy-succinimide, and the various cleavage reagents, to carry outreaction in solution, with subsequent isolation and purification ofintermediates, is well known classical peptide methodology. Classicalsolution synthesis is described in detail in the treatise, “Methoden derOrganischen Chemie (Houben-Weyl): Synthese von Peptiden,” (1974).

[0045] Techniques of exclusively solid-phase synthesis are set forth inthe textbook, “Solid-Phase Peptide Synthesis,” (Stewart and Young,1969), and are exemplified by the disclosure of U.S. Pat. No. 4,105,603(Vale et al., 1978). The fragment condensation method of synthesis isexemplified in U.S. Pat. No. 3,972,859 (1976). Other available synthesesare exemplified by U.S. Pat. Nos. 3,842,067 (1974) and 3,862,925 (1975).The synthesis of peptides containing γ-carboxyglutamic acid residues isexemplified by Rivier et al. (1987), Nishiuchi et al. (1993) and Zhou etal. (1996).

[0046] Common to such chemical syntheses is the protection of the labileside chain groups of the various amino acid moieties with suitableprotecting groups which will prevent a chemical reaction from occurringat that site until the group is ultimately removed. Usually also commonis the protection of an α-amino group on an amino acid or a fragmentwhile that entity reacts at the carboxyl group, followed by theselective removal of the α-amino protecting group to allow subsequentreaction to take place at that location. Accordingly, it is common that,as a step in such a synthesis, an intermediate compound is producedwhich includes each of the amino acid residues located in its desiredsequence in the peptide chain with appropriate side-chain protectinggroups linked to various ones of the residues having labile side chains.

[0047] As far as the selection of a side chain amino protecting group isconcerned, generally one is chosen which is not removed duringdeprotection of the α-amino groups during the synthesis. However, forsome amino acids, e.g., His, protection is not generally necessary. Inselecting a particular side chain protecting group to be used in thesynthesis of the peptides, the following general rules are followed: (a)the protecting group preferably retains its protecting properties and isnot split off under coupling conditions, (b) the protecting group shouldbe stable under the reaction conditions selected for removing theα-amino protecting group at each step of the synthesis, and (c) the sidechain protecting group must be removable, upon the completion of thesynthesis containing the desired amino acid sequence, under reactionconditions that will not undesirably alter the peptide chain.

[0048] It should be possible to prepare many, or even all, of thesepeptides using recombinant DNA technology. However, when peptides arenot so prepared, they are preferably prepared using the Merrifieldsolid-phase synthesis, although other equivalent chemical synthesesknown in the art can also be used as previously mentioned. Solid-phasesynthesis is commenced from the C-terminus of the peptide by coupling aprotected α-amino acid to a suitable resin. Such a starting material canbe prepared by attaching an α-amino-protected amino acid by an esterlinkage to a chloromethylated resin or a hydroxymethyl resin, or by anamide bond to a benzhydrylamine (BHA) resin or paramethylbenzhydrylamine(MBHA) resin. Preparation of the hydroxymethyl resin is described byBodansky et al. (1966). Chloromethylated resins are commerciallyavailable from Bio Rad Laboratories (Richmond, Calif.) and from Lab.Systems, Inc. The preparation of such a resin is described by Stewartand Young (1969). BHA and MBHA resin supports are commerciallyavailable, and are generally used when the desired polypeptide beingsynthesized has an unsubstituted amide at the C-terminus. Thus, solidresin supports may be any of those known in the art, such as one havingthe formulae —O—CH₂-resin support, —NH BHA resin support, or —NH—MBHAresin support. When the unsubstituted amide is desired, use of a BHA orMBHA resin is preferred, because cleavage directly gives the amide. Incase the N-methyl amide is desired, it can be generated from an N-methylBHA resin. Should other substituted amides be desired, the teaching ofU.S. Pat. No. 4,569,967 (Kornreich et al., 1986) can be used, or shouldstill other groups than the free acid be desired at the C-terminus, itmay be preferable to synthesize the peptide using classical methods asset forth in the Houben-Weyl text (1974).

[0049] The C-terminal amino acid, protected by Boc or Fmoc and by aside-chain protecting group, if appropriate, can be first coupled to achloromethylated resin according to the procedure set forth in K. Horikiet al. (1978), using KF in DMF at about 60° C. for 24 hours withstirring, when a peptide having free acid at the C-terminus is to besynthesized. Following the coupling of the BOC-protected amino acid tothe resin support, the α-amino protecting group is removed, as by usingtrifluoroacetic acid (TFA) in methylene chloride or TFA alone. Thedeprotection is carried out at a temperature between about 0° C. androom temperature. Other standard cleaving reagents, such as HCl indioxane, and conditions for removal of specific α-amino protectinggroups may be used as described in Schroder & Lubke (1965).

[0050] After removal of the α-amino-protecting group, the remainingα-amino- and side chain-protected amino acids are coupled step-wise inthe desired order to obtain the intermediate compound definedhereinbefore, or as an alternative to adding each amino acid separatelyin the synthesis, some of them may be coupled to one another prior toaddition to the solid phase reactor. Selection of an appropriatecoupling reagent is within the skill of the art. Particularly suitableas a coupling reagent is N,N′-dicyclohexylcarbodiimide (DCC, DIC, HBTU,HATU, TBTU in the presence of HoBt or HoAt).

[0051] The activating reagents used in the solid phase synthesis of thepeptides are well known in the peptide art. Examples of suitableactivating reagents are carbodiimides, such asN,N′-diisopropylcarbodiimide andN-ethyl-N′-(3-dimethylaminopropyl)carbodiimide. Other activatingreagents and their use in peptide coupling are described by Schroder &Lubke (1965) and Kapoor (1970).

[0052] Each protected amino acid or amino acid sequence is introducedinto the solid-phase reactor in about a twofold or more excess, and thecoupling may be carried out in a medium of dimethylformamide(DMF):CH₂Cl₂ (1:1) or in DMF or CH₂Cl₂ alone. In cases whereintermediate coupling occurs, the coupling procedure is repeated beforeremoval of the α-amino protecting group prior to the coupling of thenext amino acid. The success of the coupling reaction at each stage ofthe synthesis, if performed manually, is preferably monitored by theninhydrin reaction, as described by Kaiser et al. (1970). Couplingreactions can be performed automatically, as on a Beckman 990 automaticsynthesizer, using a program such as that reported in Rivier et al.(1978).

[0053] After the desired amino acid sequence has been completed, theintermediate peptide can be removed from the resin support by treatmentwith a reagent, such as liquid hydrogen fluoride or TFA (if using Fmocchemistry), which not only cleaves the peptide from the resin but alsocleaves all remaining side chain protecting groups and also the -aminoprotecting group at the N-terminus if it was not previously removed toobtain the peptide in the form of the free acid. If Met is present inthe sequence, the Boc protecting group is preferably first removed usingtrifluoroacetic acid (TFA)/ethanedithiol prior to cleaving the peptidefrom the resin with HF to eliminate potential S-alkylation. When usinghydrogen fluoride or TFA for cleaving, one or more scavengers such asanisole, cresol, dimethyl sulfide and methylethyl sulfide are includedin the reaction vessel.

[0054] Cyclization of the linear peptide is preferably affected, asopposed to cyclizing the peptide while a part of the peptido-resin, tocreate bonds between Cys residues. To effect such a disulfide cyclizinglinkage, fully protected peptide can be cleaved from a hydroxymethylatedresin or a chloromethylated resin support by ammonolysis, as is wellknown in the art, to yield the fully protected amide intermediate, whichis thereafter suitably cyclized and deprotected. Alternatively,deprotection, as well as cleavage of the peptide from the above resinsor a benzhydrylamine (BHA) resin or a methylbenzhydrylamine (MBHA), cantake place at 0° C. with hydrofluoric acid (HF) or TFA, followed byoxidation as described above.

[0055] The peptides are also synthesized using an automatic synthesizer.Amino acids are sequentially coupled to an MBHA Rink resin (typically100 mg of resin) beginning at the C-terminus using an Advanced Chemtech357 Automatic Peptide Synthesizer. Couplings are carried out using1,3-diisopropylcarbodimide in N-methylpyrrolidinone (NMP) or by2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate(HBTU) and diethylisopropylethylamine (DIEA). The FMOC protecting groupis removed by treatment with a 20% solution of piperidine indimethylformamide(DMF). Resins are subsequently washed with DMF (twice),followed by methanol and NMP.

[0056] Muteins, analogs or active fragments, of the foregoing conotoxinpeptides are also contemplated here. See, e.g., Hammerland et al.(1992). Derivative muteins, analogs or active fragments of the conotoxinpeptides may be synthesized according to known techniques, includingconservative amino acid substitutions, such as outlined in U.S. Pat.Nos. 5,545,723 (see particularly col. 2, line 50—col. 3, line 8);5,534,615 (see particularly col. 19, line 45—col 22, line 33); and5,364,769 (see particularly col. 4, line 55—col. 7, line 26), eachherein incorporated by reference.

[0057] The ω-conopeptides of the present invention are also useful toreduce neurotoxic injury associated with conditions of hypoxia, anoxiaor ischemia which typically follows stroke, cerebrovascular accident,brain or spinal chord trauma, myocardial infarct, physical trauma,drownings, suffocation, perinatal asphyxia, or hypoglycemic events. Toreduce neurotoxic injury, an ω-conopeptide should be administered in atherapeutically effective amount to the patient within 24 hours of theonset of the hypoxic, anoxic or ischemic condition in order for theω-conopeptide to effectively minimize the CNS damage which the patientwill experience.

[0058] The ω-conopeptides of the present invention are further useful incontrolling pain, e.g., as analgesic agents, and the treatment ofmigraine, acute pain or persistent pain. They can be usedprophylactically or to relieve the symptoms associated with a migraineepisode, or to treat acute or persistent pain. For these uses, anω-conopeptide is administered in a therapeutically effective amount toovercome or to ease the pain.

[0059] Pharmaceutical compositions containing a compound of the presentinvention as the active ingredient can be prepared according toconventional pharmaceutical compounding techniques. See, for example,Remington's Pharmaceutical Sciences, 18th Ed. (1990, Mack PublishingCo., Easton, Pa.). Typically, an antagonistic amount of activeingredient will be admixed with a pharmaceutically acceptable carrier.The carrier may take a wide variety of forms depending on the form ofpreparation desired for administration, e.g., intravenous, oral,parenteral or intrathecally. For examples of delivery methods see U.S.Pat. No. 5,844,077, incorporated herein by reference.

[0060] “Pharmaceutical composition” means physically discrete coherentportions suitable for medical administration. “Pharmaceuticalcomposition in dosage unit form” means physically discrete coherentunits suitable for medical administration, each containing a daily doseor a multiple (up to four times) or a sub-multiple (down to a fortieth)of a daily dose of the active compound in association with a carrierand/or enclosed within an envelope. Whether the composition contains adaily dose, or for example, a half, a third or a quarter of a dailydose, will depend on whether the pharmaceutical composition is to beadministered once or, for example, twice, three times or four times aday, respectively.

[0061] The term “salt”, as used herein, denotes acidic and/or basicsalts, formed with inorganic or organic acids and/or bases, preferablybasic salts. While pharmaceutically acceptable salts are preferred,particularly when employing the compounds of the invention asmedicaments, other salts find utility, for example, in processing thesecompounds, or where non-medicament-type uses are contemplated. Salts ofthese compounds may be prepared by art-recognized techniques.

[0062] Examples of such pharmaceutically acceptable salts include, butare not limited to, inorganic and organic addition salts, such ashydrochloride, sulphates, nitrates or phosphates and acetates,trifluoroacetates, propionates, succinates, benzoates, citrates,tartrates, fumarates, maleates, methane-sulfonates, isothionates,theophylline acetates, salicylates, respectively, or the like. Loweralkyl quaternary ammonium salts and the like are suitable, as well.

[0063] As used herein, the term “pharmaceutically acceptable” carriermeans a non-toxic, inert solid, semi-solid liquid filler, diluent,encapsulating material, formulation auxiliary of any type, or simply asterile aqueous medium, such as saline. Some examples of the materialsthat can serve as pharmaceutically acceptable carriers are sugars, suchas lactose, glucose and sucrose, starches such as corn starch and potatostarch, cellulose and its derivatives such as sodium carboxymethylcellulose, ethyl cellulose and cellulose acetate; powdered tragacanth;malt, gelatin, talc; excipients such as cocoa butter and suppositorywaxes; oils such as peanut oil, cottonseed oil, safflower oil, sesameoil, olive oil, corn oil and soybean oil; glycols, such as propyleneglycol, polyols such as glycerin, sorbitol, mannitol and polyethyleneglycol; esters such as ethyl oleate and ethyl laurate, agar; bufferingagents such as magnesium hydroxide and aluminum hydroxide; alginic acid;pyrogen-free water; isotonic saline, Ringer's solution; ethyl alcoholand phosphate buffer solutions, as well as other non-toxic compatiblesubstances used in pharmaceutical formulations.

[0064] Wetting agents, emulsifiers and lubricants such as sodium laurylsulfate and magnesium stearate, as well as coloring agents, releasingagents, coating agents, sweetening, flavoring and perfuming agents,preservatives and antioxidants can also be present in the composition,according to the judgment of the formulator. Examples ofpharmaceutically acceptable antioxidants include, but are not limitedto, water soluble antioxidants such as ascorbic acid, cysteinehydrochloride, sodium bisulfite, sodium metabisulfite, sodium sulfite,and the like; oil soluble antioxidants, such as ascorbyl palmitate,butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT),lecithin, propyl gallate, aloha-tocopherol and the like; and the metalchelating agents such as citric acid, ethylenediamine tetraacetic acid(EDTA), sorbitol, tartaric acid, phosphoric acid and the like.

[0065] For oral administration, the compounds can be formulated intosolid or liquid preparations such as capsules, pills, tablets, lozenges,melts, powders, suspensions or emulsions.

[0066] In preparing the compositions in oral dosage form, any of theusual pharmaceutical media may be employed, such as, for example, water,glycols, oils, alcohols, flavoring agents, preservatives, coloringagents, suspending agents, and the like in the case of oral liquidpreparations (such as, for example, suspensions, elixirs and solutions);or carriers such as starches, sugars, diluents, granulating agents,lubricants, binders, disintegrating agents and the like in the case oforal solid preparations (such as, for example, powders, capsules andtablets). Because of their ease in administration, tablets and capsulesrepresent the most advantageous oral dosage unit form, in which casesolid pharmaceutical carriers are obviously employed. If desired,tablets may be sugar-coated or enteric-coated by standard techniques.The active agent can be encapsulated to make it stable to passagethrough the gastrointestinal tract while at the same time allowing forpassage across the blood brain barrier. See for example, WO 96/11698.

[0067] For parenteral administration, the compound may be dissolved in apharmaceutical carrier and administered as either a solution or asuspension. Illustrative of suitable carriers are water, saline,dextrose solutions, fructose solutions, ethanol, or oils of animal,vegetative or synthetic origin. The carrier may also contain otheringredients, for example, preservatives, suspending agents, solubilizingagents, buffers and the like. When the compounds are being administeredintrathecally, they may also be dissolved in cerebrospinal fluid.

[0068] A variety of administration routes are available. The particularmode selected will depend of course, upon the particular drug selected,the severity of the disease state being treated and the dosage requiredfor therapeutic efficacy. The methods of this invention, generallyspeaking, may be practiced using any mode of administration that ismedically acceptable, meaning any mode that produces effective levels ofthe active compounds without causing clinically unacceptable adverseeffects. Such modes of administration include oral, rectal, sublingual,topical, nasal, transdermal or parenteral routes. The term “parenteral”includes subcutaneous, intravenous, epidural, irrigation, intramuscular,release pumps, or infusion.

[0069] For example, administration of the active agent according to thisinvention may be achieved using any suitable delivery means, including:

[0070] (a) pump (see, e.g., Luer & Hatton (1993), Zimm et al. (1984) andEttinger et al. (1978));

[0071] (b), microencapsulation (see, e.g., U.S. Pat. Nos. 4,352,883;4,353,888; and 5,084,350);

[0072] (c) continuous release polymer implants (see, e.g., U.S. Pat. No.4,883,666);

[0073] (d) macroencapsulation (see, e.g., U.S. Pat. Nos. 5,284,761,5,158,881, 4,976,859 and 4,968,733 and published PCT patent applicationsWO92/19195, WO 95/05452);

[0074] (e) naked or unencapsulated cell grafts to the CNS (see, e.g.,U.S. Pat. Nos. 5,082,670 and 5,618,531);

[0075] (f) injection, either subcutaneously, intravenously,intra-arterially, intramuscularly, or to other suitable site; or

[0076] (g) oral administration, in capsule, liquid, tablet, pill, orprolonged release formulation.

[0077] In one embodiment of this invention, an active agent is delivereddirectly into the CNS, preferably to the brain ventricles, brainparenchyma, the intrathecal space or other suitable CNS location, mostpreferably intrathecally.

[0078] Alternatively, targeting therapies may be used to deliver theactive agent more specifically to certain types of cell, by the use oftargeting systems such as antibodies or cell specific ligands. Targetingmay be desirable for a variety of reasons, e.g. if the agent isunacceptably toxic, or if it would otherwise require too high a dosage,or if it would not otherwise be able to enter the target cells.

[0079] The active agents, which are peptides, can also be administeredin a cell based delivery system in which a DNA sequence encoding anactive agent is introduced into cells designed for implantation in thebody of the patient, especially in the spinal cord region.

[0080] Suitable delivery systems are described in U.S. Pat. No.5,550,050 and published PCT Application Nos. WO 92/19195, WO 94/25503,WO 95/01203, WO 95/05452, WO 96/02286, WO 96/02646, WO 96/40871, WO96/40959 and WO 97/12635. Suitable DNA sequences can be preparedsynthetically for each active agent on the basis of the developedsequences and the known genetic code.

[0081] The active agent is preferably administered in an therapeuticallyeffective amount. By a “therapeutically effective amount” or simply“effective amount” of an active compound is meant a sufficient amount ofthe compound to treat the desired condition at a reasonable benefit/riskratio applicable to any medical treatment. The actual amountadministered, and the rate and time-course of administration, willdepend on the nature and severity of the condition being treated.Prescription of treatment, e.g. decisions on dosage, timing, etc., iswithin the responsibility of general practitioners or spealists, andtypically takes account of the disorder to be treated, the condition ofthe individual patient, the site of delivery, the method ofadministration and other factors known to practitioners. Examples oftechniques and protocols can be found in Remington 's ParmaceuticalSciences.

[0082] Dosage may be adjusted appropriately to achieve desired druglevels, locally or systemically. Typically the active agents of thepresent invention exhibit their effect at a dosage range from about0.001 mg/kg to about 250 mg/kg, preferably from about 0.01 mg/kg toabout 100 mg/kg of the active ingredient, more preferably from a bout0.05 mg/kg to about 75 mg/kg. A suitable dose can be administered inmultiple sub-doses per day. Typically, a dose or sub-dose may containfrom about 0.1 mg to about 500 mg of the active ingredient per unitdosage form. A more preferred dosage will contain from about 0.5 mg toabout 100 mg of active ingredient per unit dosage form. Dosages aregenerally initiated at lower levels and increased until desired effectsare achieved. In the event that the response in a subject isinsufficient at such doses, even higher doses (or effective higher dosesby a different, more localized delivery route) may be employed to theextent that patient tolerance permits. Continuous dosing over, forexample 24 hours or multiple doses per day are contemplated to achieveappropriate systemic levels of compounds.

[0083] For the treatment of pain, if the route of administration isdirectly to the CNS, the dosage contemplated is from about 1 ng to about100 mg per day, preferably from about 100 ng to about 10 mg per day,more preferably from about 1 μg to about 100 μg per day. If administeredperipherally, the dosage contemplated is somewhat higher, from about 100ng to about 1000 mg per day, preferably from about 10 μg to about 100 mgper day, more preferably from about 100 μg to about 10 mg per day. Ifthe conopeptide is delivered by continuous infusion (e.g., by pumpdelivery, biodegradable polymer delivery or cell-based delivery), then alower dosage is contemplated than for bolus delivery.

[0084] Advantageously, the compositions are formulated as dosage units,each unit being adapted to supply a fixed dose of active ingredients.Tablets, coated tablets, capsules, ampoules and suppositories areexamples of dosage forms according to the invention.

[0085] It is only necessary that the active ingredient constitute aneffective amount, i.e., such that a suitable effective dosage will beconsistent with the dosage form employed in single or multiple unitdoses. The exact individual dosages, as well as daily dosages, aredetermined according to standard medical principles under the directionof a physician or veterinarian for use humans or animals.

[0086] The pharmaceutical compositions will generally contain from about0.0001 to 99 wt. %, preferably about 0.001 to 50 wt. %, more preferablyabout 0.01 to 10 wt. % of the active ingredient by weight of the totalcomposition. In addition to the active agent, the pharmaceuticalcompositions and medicaments can also contain other pharmaceuticallyactive compounds. Examples of other pharmaceutically active compoundsinclude, but are not limited to, analgesic agents, cytokines andtherapeutic agents in all of the major areas of clinical medicine. Whenused with other pharmaceutically active compounds, the conopeptides ofthe present invention may be delivered in the form of drug cocktails. Acocktail is a mixture of any one of the compounds useful with thisinvention with another drug or agent. In this embodiment, a commonadministration vehicle (e.g., pill, tablet, implant, pump, injectablesolution, etc.) would contain both the instant composition incombination supplementary potentiating agent. The individual drugs ofthe cocktail are each administered in therapeutically effective amounts.A therapeutically effective amount will be determined by the parametersdescribed above; but, in any event, is that amount which establishes alevel of the drugs in the area of body where the drugs are required fora period of time which is effective in attaining the desired effects.

[0087] The practice of the present invention employs, unless otherwiseindicated, conventional techniques of chemistry, molecular biology,microbiology, recombinant DNA, genetics, immunology, cell biology, cellculture and transgenic biology, which are within the skill of the art.See, e.g., Maniatis et al., 1982; Sambrook et al., 1989; Ausubel et al.,1992;

[0088] Glover, 1985; Anand, 1992; Guthrie and Fink, 1991; Harlow andLane, 1988; Jakoby and Pastan, 1979; Nucleic Acid Hybridization (B. D.Hames & S. J. Higgins eds. 1984);

[0089]Transcription And Translation (B. D. Hames & S. J. Higgins eds.1984); Culture Of Animal Cells (R. I. Freshney, Alan R. Liss, Inc.,1987); Immobilized Cells And Enzymes (IRL Press, 1986); B. Perbal, APractical Guide To Molecular Cloning (1984); the treatise, Methods InEnzymology (Academic Press, Inc., N.Y.); Gene Transfer Vectors ForMammalian Cells (J. H. Miller and M. P. Calos eds., 1987, Cold SpringHarbor Laboratory); Methods In Enzymology, Vols. 154 and 155 (Wu et al.eds.), Immunochemical Methods In Cell And Molecular Biology (Mayer andWalker, eds., Academic Press, London, 1987); Handbook Of ExperimentalImmunology, Volumes I-IV (D. M. Weir and C. C. Blackwell, eds., 1986);Riott, Essential Immunology, 6th Edition, Blackwell ScientificPublications, Oxford, 1988; Hogan et al., Manipulating the Mouse Embryo,(Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1986).

EXAMPLES

[0090] The present invention is described by reference to the followingExamples, which are offered by way of illustration and are not intendedto limit the invention in any manner.

[0091] Standard techniques well known in the art or the techniquesspecifically described below were utilized.

Example 1 Isolation of ω-Conotoxins

[0092] Crude venom was extracted from venom ducts (Cruz et al., 1976),and the components were purified as previously described (Cartier etal., 1996). The crude extract from venom ducts was purified by reversephase liquid chromatography (RPLC) using a Vydac C₁₈ semi-preparativecolumn (10×250 mm). Further purification of bioactive peaks was done ona Vydac C₁₈ analytical column (4.6×220 mm). The effluents were monitoredat 220 nm. Peaks were collected, and aliquots were assayed for activity.Throughout purification, HPLC fractions were assayed by means ofintracerebral ventricular (i.c.v.) injection into mice (Clark et al.,1981).

[0093] The amino acid sequence of the purified peptides were determinedby standard methods. The purified peptides were reduced and alkylatedprior to sequencing by automated Edman degradation on an AppliedBiosystems 477A Protein Sequencer with a 120A Analyzer (DNA/PeptideFacility, University of Utah) (Martinez et al., 1995; Shon et al.,1994).

[0094] In accordance with this method, the ω-conopeptides described as“isolated” in Table 1 were obtained. These ω-conopeptides, as well asthe other ω-conopeptides and the ω-conopeptide precursors set forth inTable 1 are synthesized as described in U.S. Pat. No. 5,591,821.

Example 2

[0095] Isolation of DNA Encoding ω-Conopeotides

[0096] DNA coding for ω-conopeptides was isolated and cloned inaccordance with conventional techniques using general procedures wellknown in the art, such as described in Olivera et al. (1996).Alternatively, cDNA libraries was prepared from Conus venom duct usingconventional techniques. DNA from single clones was amplified byconventional techniques using primers which correspond approximately tothe M13 universal priming site and the M13 reverse universal primingsite. Clones having a size of approximately 300-500 nucleotides weresequenced and screened for similarity in sequence to known ω-conotoxins.The DNA sequences and encoded propeptide sequences are set forth inTable 1. DNA sequences coding for the mature toxin can also be preparedon the basis of the DNA sequences set forth in Table1. An alignment ofthe ω-conopeptides of the present invention is set forth in Table 2.TABLE 1 DNA and Amino Acid Sequences of ω-Conopeptides and PrecursorsName: J410 Species: Cloned: Yes DNA Sequence:GGATCCATGAAACTGACGTGCATGGTGATCGTCGCCGTGCTGCTCCTGACGGCCTGT (SEQ ID NO:1)CAACTCATCACAGCTGATGACTCCAGAGGTACGCAGAAGCATCATGCCCTGAGGTCGACCACCAATTTCTCCACGTTGACTCGTCGCTGCCTTTCTCCCGGATCACGATGTCATAAGACAATGCGTAACTGCTGCACTTCATGCTCTTCATACAAAGGGAAATGTCGGCCTCGAAAATGAACCACTCATCACCTACTCCTCTGGAGGCCTCAGAGGAATTACATTGAAATAAAAGCCGCATTACAAAAAAAAAAAAAAAAA Translation:MKLTCMVIVAVLLLTACQLITADDSRGTQKHHALRSTTNFSTLTRRCLSPGSRCHKTMR (SEQ IDNO:2) NCCTSCSSYKGKCRPRK Toxin Sequence:Cys-Leu-Ser-Xaa3-Gly-Ser-Arg-Cys-His-Lys-Thr-Met-Arg-Asn-Cys-Cys-Thr-Ser-Cys-Ser-Ser-(SEQ ID NO:3) Xaa5-Lys-Gly-Lys-Cys-Arg-Xaa3-Arg-Lys-{circumflex over( )} Name: J411 Species: Cloned: Yes DNA Sequence:GGATCCATGAAACTGACGTGCGTGGTGATCGTCGCCGTGCTGCTCCTGACGGTCTGT (SEQ ID NO:4)CAACTCATCACAGCTGATGACTCCAGAGGTACGCAGAAGCATCATGCCCTGAGGTCGACCACCAATTTCTCCACGTCGACTCGTCGCTGCAAACCTCCCGGAAGAAAATGTCTGAATAGAAAGAATGAATGCTGCAGCAAGTTTTGCAATGAACACCTACATATGTGTGGATAAATGGCTAAAAACTGAATAAAAGCCGCATTGCAAAAAAAAAAAAAAAAAAA AA Translation:MKLTCVVIVAVLLLTVCQLITADDSRGTQKHHALRSTTNFSTSTRRCKPPGRKCLNRKN (SEQ IDNO:5) ECCSKFCNEHLHMCG Toxin Sequence:Cys-Lys-Xaa3-Xaa3-Gly-Arg-Lys-Cys-Leu-Asn-Arg-Lys-Asn-Xaa1-Cys-Cys-Ser-Lys-Phe-(SEQ ID NO:6) Cys-Asn-Xaa1-His-Leu-His-Met-Cys-# Name: J413 Species:Cloned: Yes DNA Sequence:GGATCCATGAAACTGACGTGCGTGGTGATCGTCGCCGTGCTGCTCCTGACGGCCTGT (SEQ ID NO:7)CAACTCGTCACAGCTGATGGCTCCAGAGGTATGCAGAAGCATTATGCCCTGAGGTCGACCACCAATCTCTCCATATCGTCTCGCTGCAAACCTCCCAGAAGAAAATGTCTGAAGATTAAGGATAAATGCTGCAACTTTTGCAATACACACCTAAATATGTGTGGATAAATGGCTAAAAACTGAATAAAAGCCGCATTGCAAAAAAAAAAAAAAAAAAA Translation:MKLTCVVIVAVLLLTACQLVTADGSRGMQKHYALRSTTNLSISSRCKPPRRKCLKIKDK (SEQ IDNO:8) CCNFCNTHLNMCG Toxin Sequence:Cys-Lys-Xaa3-Xaa3-Arg-Arg-Lys-Cys-Leu-Lys-Ile-Lys-Asp-Lys-Cys-Cys-Asn-Phe-Cys-Asn-(SEQ ID NO:9) Thr-His-Leu-Asn-Met-Cys-# Name: J414 Species: Cloned: YesDNA Sequence: GGATCCATGAAACTGACGTGTGTGGTGATCGTCGCCGTGCTGCTCCTGATGGCCTGT(SEQ ID NO:10) CAACTCGTCACAGCTGATGGCTCCAGAGGTATGCACAAGCATTATGCCCTGAGGTCGACCACCAAACTCTCCATGTCGACTCGCTGCGCAGGTCCAGGAACAATTTGTCCTAATAGGGTATGCTGCGGTTATTGCAGTAAAAGAACACATCTATGTCATTCGCGAACTGGCTGATCTTCCCCCTTCTGCGCTCCATCCTTTTCTGCCTGAGTCCTCCATACCTGAGAATGGTCATGAACCACTCAACACCTACTCCTCTGGAGGGCCTCAGAAGAGCTACATTGAAATAAAAGCCGCATTACAAAAAAAAAAAAAAAAAA Translation:MKLTCVVIVAVLLLMACQLVTADGSRGMHKHYALRSTTKLSMSTRCAGPGTICPNRVC (SEQ IDNO:11) CGYCSKRTHLCHSRTG Toxin Sequence:Cys-Ala-Gly-Xaa3-Gly-Thr-Ile-Cys-Xaa3-Asn-Arg-Val-Cys-Cys-Gly-Xaa5-Cys-Ser-Lys-Arg-(SEQ ID NO:12) Thr-His-Leu-Cys-His-Ser-Arg-Thr-# Name: Ar6.10 Species:arenatus Cloned: Yes DNA Sequence:GGATCCATGAAACTGACGTGCATGGTGATCATCGCCGTGCTGTTCCTGACGGCCTGT (SEQ ID NO:13)CAACTCATTACAGGTGAGCAGAAGGACCATGCTCTGAGGTCAACTGACAAAAACTCCAAGTTGACTAGGCAGTGCTCGGCTAACGGTGGATCTTGTACTCGTCATTTTCACTGCTGCAGCCTCTATTGCAATAAAGATTCCAGTGTATGTGTGGCAACCTCATACCCGTGAGTGGCCATGAACCCCTCAATACCCTCTCCTCTGGAGGCTTCAGAGGAACTGCATTGAAATAAAACCGCATTGCAATAAAAAAAAAAAAAAAAAAA Translation:MKLTCMVIIAVLFLTACQLITGEQKDHALRSTDKNSKLTRQCSANGGSCTRHFHCCSLY (SEQ IDNO:14) CNKDSSVCVATSYP Toxin Sequence:Xaa2-Cys-Ser-Ala-Asn-Gly-Gly-Ser-Cys-Thr-Arg-His-Phe-His-Cys-Cys-Ser-Leu-Xaa5-Cys-(SEQ ID NO:15)Asn-Lys-Asp-Ser-Ser-Val-Cys-Val-Ala-Thr-Ser-Xaa5-Xaa3-{circumflex over( )} Name: Ar6.2 Species: arenatus Cloned: Yes DNA Sequence:ACCAAAACCATCATCAAAATGAAACTGACGTGCGTGTTGATTATCGCCGTGCTGTTC (SEQ ID NO:16)CTGACGGCCTGTCAACTCATTACAGCTGAGACTTACTCCAGAGGTGAGCAGAAGCACCATGCTCTGAGGTCAACTGACAGAAACTCCAAGTTGACCAGGACATGCAACACTCCCACTGAATATTGTACTTTGCATCGACACTGCTGCAGCGGCTACTGCCATAAAACAATCCAGGCATGTTCATAATACCGGTGAGTGGTCATGAACCACTCAATACCCTCTCCTCTGGAGGCTTCAGAGGAACTGCATTGAAATAAAAGCCGCATTGC Translation:MKLTCVLIIAVLFLTACQLITAETYSRGEQKHHALRSTDRNSKLTRTCNTPTEYCTLHRH (SEQ IDNO:17) CCSGYCHKTIQACS Toxin Sequence:Thr-Cys-Asn-Thr-Xaa3-Thr-Xaa1-Xaa5-Cys-Thr-Leu-His-Arg-His-Cys-Cys-Ser-Gly-Xaa5-(SEQ ID NO:18) Cys-His-Lys-Thr-Ile-Gln-Ala-Cys-Ser-{circumflex over ( )}Name: Ar6.3 Species: arenatus Cloned: Yes DNA Sequence:ACCAAAACCATCATCAAAATGAAACTGACGTGCGTGTTGATCATCGCCGTGCTGTTC (SEQ ID NO:19)CTGACGGCCTGTCAACTCATTACAGCTGAGACTTACTCCAGAGGTGAGCAGATGCACCGTGCTCTGAGGTCAACTGACAAAAACTCCAAGTTGACTAGGCAGTGCACGCCTAACGGTGGATCTTGTTCTCGTCATTTTCACTGCTGCAGCCTCTATTGCAATAAAAGTACTGGCGTATGTATTGCAACCTCATACCCGTGAGTGGTCATGAACCACTCAATACCCTCTCCTCTGGAGGCTTCAGAGGAACTGCATTGAAATAAAAGCCGCATTGC Translation:MRLTCVLIIAVLFLTACQLITAETYSRGEQMHRALRSTDKNSKLTRQCTPNGGSCSRHF (SEQ IDNO:20) HCCSLYCNKSTGVCIATSYP Toxin Sequence:Xaa2-Cys-Thr-Xaa3-Asn-Gly-Gly-Ser-Cys-Ser-Arg-His-Phe-His-Cys-Cys-Ser-Leu-Xaa5-Cys-(SEQ ID NO:21)Asn-Lys-Ser-Thr-Gly-Val-Cys-Ile-Ala-Thr-Ser-Xaa5-Xaa3-{circumflex over( )} Name: Ar6.4 Species: arenatus Cloned: Yes DNA Sequence:GGATCCATGAAACTGACGTGCATGGTGATTATCGCCGTGCTGTTCCTGACGGCCTGT (SEQ ID NO:22)CAACTCATTACAGCTGAGACTTACTCCAGAGGTGAGCAGAAGCACCATGCTCTGAGGTCAACTGACAAAAACTCCAAGTTGACCAGGACATGCAACACTCCCACCGAATATTGTACTTTGCATCAACACTGCTGCAGCGGCTACTGCCATAAAACAATCCAGGCATGTTCATAATACCGGTGAGTGGTCATGAACCACTCAATACCCTCTCCTCTGGAGGCTTCAGAGGAACTGCATTGAAATAAAACCGCATTACAAAAAAAAAAAAAAAAAAA Translation:MKLTCMVIIAVLFLTACQLITAETYSRGEQKHHALRSTDKNSKLTRTCNTPTEYCTLHQ (SEQ IDNO:23) HCCSGYCHKTIQACS Toxin Sequence:Thr-Cys-Asn-Thr-Xaa3-Thr-Xaa1-Xaa5-Cys-Thr-Leu-His-Gln-His-Cys-Cys-Ser-Gly-Xaa5-(SEQ ID NO:24) Cys-His-Lys-Thr-Ile-Gln-Ala-Cys-Ser- Name: Ar6.6 Species:arenatus Cloned: Yes DNA Sequence:GGATCCATGAAACTGACGTGTATGGTGATCATCGCCGTACTGTTCCTGACGGCCTGT (SEQ ID NO:25)CAACTCATTACAGCTGAGACTTACTCCAGAGGTAAGCAGATGCACCGCGCTCTGAGGTCAACTGACAAAAACTCCCAGTTGACCAGGGAATGCACACCTCCCGGTGGAGCTTGTGGTTTACCTACACACTGCTGCGGGTTTTGCGATACTGCAAACAACAGATGTCTGTAAAGCTGGTCTGGCGTCTGATATTCCCCTTCTGTGCTCTATCCTCTTTGGCCTGAGTCATCCGTACCTGTGAGTGGTCATGAACTACTCAATACCCTCTCCTCTGGAGGCTTCAGAGGAACTACAATGAAATAAAACCCGCATTGCAGAGAAAAAAAAAAAAAAAAAA Translation:MKLTCMVIIAVLFLTACQLITAETYSRGKQMHRALRSTDKNSQLTRECTPPGGACGLPT (SEQ IDNO:26) HCCGFCDTANNRCL Toxin Sequence:Xaa1-Cys-Thr-Xaa3-Xaa3-Gly-Gly-Ala-Cys-Gly-Leu-Xaa3-Thr-His-Cys-Cys-Gly-Phe-Cys-(SEQ ID NO:27) Asp-Thr-Ala-Asn-Asn-Arg-Cys-Leu-{circumflex over ( )}Name: Ar6.7 Species: arenatus Cloned: Yes DNA Sequence:GGATCCATGAAACTGACGTGCGTGGTGATTATCGCCGTGCTGTTCCTGACGGCCTGT (SEQ ID NO:28)CAACTCATTACAGCTGAGACTTACTCCAGAGGTGAGCAGAATCACCATGTTCTGAGGTCAACTGACAAAAACTCCAAGTTGACCAGGACATGCAACACTCCCACTGAATATTGTACTTTGCATCAACACTGCTGCAGCGGCCACTGCCATAAAACAATCCAGGCATGTGCATAATACCGGTGGGTGGTCATGAACCACTCAATACCCTCTCCTCTGGAGGCTTCAGAGGAACTGCATTGAAATAAAACCGCATTGCAATGAANAAAAAAAAAAAAAAAAA AAAAAAAATranslation: MKLTCVVIIAVLFLTACQLITAETYSRGEQNHHVLRSTDKNSKLTRTCNTPTEYCTLHQ(SEQ ID NO:29) HCCSGHCHKTIQACA Toxin Sequence:Thr-Cys-Asn-Thr-Xaa3-Thr-Xaa1-Xaa5-Cys-Thr-Leu-His-Gln-His-Cys-Cys-Ser-Gly-His-Cys-(SEQ ID NO:30) His-Lys-Thr-Ile-Gln-Ala-Cys-Ala-{circumflex over ( )}Name: Ar6.8 Species: arenatus Cloned: Yes DNA Sequence:GGATCCATGAAACTGACGTGTGTGGTGATCATCGCCGTGCTGTTCCTGACGGCCTGT (SEQ ID NO:31)CAACTCACTACAGGTGAGCAGAAGGACCATGCTCTGAGGTCAACTGACAAAAACTCCAAGTTGACTAGGCAGTGCTCGCCTATCGGTGGATATTGTACTCTTCATATTCACTGCTGCAGCAACCATTGCATTAAACCTATCGGCCGATGTGTGGCAACCTGATACCCGTGCGTGGTCATGAACCCCTCAATACCCTCTCCTCTGGAGGCTTCAGAGGAACTGCATTGAAATAAAACCGCATTGCAATAAAAAAAAAAAAAAAAAA Translation:MKLTCVVIIAVLFLTACQLTTGEQKDHALRSTDKNSKLTRQCSPIGGYCTLHIHCCSNHC (SEQ IDNO:32) IKPIGRCVAT Toxin Sequence:Xaa2-Cys-Ser-Xaa3-Ile-Gly-Gly-Xaa5-Cys-Thr-Leu-His-Ile-His-Cys-Cys-Ser-Asn-His-Cys-(SEQ ID NO:33) Ile-Lys-Xaa3-Ile-Gly-Arg-Cys-Val-Ala-Thr-{circumflex over( )} Name: Ar6.9 Species: arenatus Cloned: Yes DNA Sequence:GGATCCATGAAACTGACGTGCGTGGTGATCATCGCCGTGCTGTTCCTGACGGCCTGT (SEQ ID NO:34)CAACTCACTACAGGTGAGCAGAAGGACCATGCTCTGAGGTCAACTGACAAAAACTCCAAGTTGACTAGGCAGTGCTTGCCTAACGGTGGATATTGTACTCTTCATATTCACTGCTGCAGCGACCATTGCATTAAACCTATCGACCGATGTGTGGCAACCTGATACCCGGGCGTGGTCATGAACCCCTCAATACCCTCTCCTCTGGAGGCTTCAGAGGAACTGCATTGAAATAAAACCGCATTACAAAAAAAAAAAAAAAAA Translation:MKLTCVVIIAVLFLTACQLTTGEQKDHALRSTDKNSKLTRQCLPNGGYCTLHIHCCSDH (SEQ IDNO:35) CIKPIDRCVAT Toxin Sequence:Xaa2-Cys-Leu-Xaa3-Asn-Gly-Gly-Xaa5-Cys-Thr-Leu-His-Ile-His-Cys-Cys-Ser-Asp-His-Cys-(SEQ ID NO:36) Ile-Lys-Xaa3-Ile-Asp-Arg-Cys-Val-Ala-Thr-{circumflex over( )} Name: Ay6.1 Species: aurisiacus Cloned: Yes DNA Sequence:ATGAAACTGACGTGTGTGGTGATCGTCGCCGTGCTGCTCCTGACGGCCTGTCAACTC (SEQ ID NO:37)ATCACAGCTGATGACTCCAGAGGTACGCAGAAGCATCGTTCCCTGAGCTCGGCCACCAAACTCTCCATGTCGACTCGCTGCAAGGGTAAAGGAAAACCATGCAGTAGGATTTCGTATAACTGCTGCACCGGTTCTTGCAGATCAGGTAAATGTGGCTGATCCAGCGCCTGATCTTCCCCCTTCTGTGCTCTATCCTTTTCTGCCTGAGTCCTCCTTACCTGAGAGTGGTCATGAACCACTCATCACCTGCTCCTCTGGAGGCCCCAGAGGAGCTACATTGAAATAAAAGTCGCATTGCAAAAAAAAAAAAAAAAAAA Translation:MKLTCVVIVAVLLLTACQLITADDSRGTQKHRSLSSATKLSMSTRCKGKGKPCSRISYN (SEQ IDNO:38) CCTGSCRSGKCG Toxin Sequence:Cys-Lys-Gly-Lys-Gly-Lys-Xaa3-Cys-Ser-Arg-Ile-Ser-Xaa5-Asn-Cys-Cys-Thr-Gly-Ser-Cys-(SEQ ID NO:39) Arg-Ser-Gly-Lys-Cys-# Name: Ay6.2 Species: aurisiacusCloned: Yes DNA Sequence:ATGAAACTGACGTGTGTGGTGATCGTCGCCGTGCTGCTCCTGACGGCCTGTCAACTC (SEQ ID NO:37)ATCACAGCTGATGACTCCAGAGGTACGCAGAAGCATCGTTCCCTGAGCTCGGCCACCAAACTCTCCATGTCGACTCGCTGCAAGGGTAAAGGAAAACCATGCAGTAGGATTTCGTATAACTGCTGCACCGGTTCTTGCAGATCAGGTAAATGTGGCTGATCCAGCGCCTGATCTTCCCCCTTCTGTGCTCTATCCTTTTCTGCCTGAGTCCTCCTTACCTGAGAGTGGTCATGAACCACTCATCACCTGCTCCTCTGGAGGCCCCAGAGGAGCTACATTGAAATAAAAGTCGCATTGCAAAAAAAAAAAAAAAAAAA Translation:MKLTCVVIVAVLLLTACQLITADDSRGTQKHRSLSSATKLSMSTRCKGKGKPCSRISYN (SEQ IDNO:38) CCTGSCRSGKCG Toxin Sequence:Cys-Lys-Gly-Lys-Gly-Lys-Xaa3-Cys-Ser-Arg-Ile-Ser-Xaa5-Asn-Cys-Cys-Thr-Gly-Ser-Cys-(SEQ ID NO:39) Arg-Ser-Gly-Lys-Cys-# Name: Ay6.2 Species: aurisiacusCloned: Yes DNA Sequence:ATGAAACTGACGTGTGTGGTGATCGTCGCCGTGCTGCTCCTGACGGCCTGTCAACTC (SEQ ID NO:40)ATCACAGCTGATGACTCCAGAGGTACGCAGAAGCATCGTTCCCTGAGGTCGAAGACCAAACTCTCCATGTCGACTGGCTGCATGGAAGCCGGATCTTATTGCGGCTCTACTACGAGAATCTGCTGCGGTTTTTGCGCTTATTTCGGCAAAAAATGTATTGACTATCCCAGCAACTGATCTTCCCCCTACTGTGCTCTATCCTTTTCTGCCTGAGTCCTCCTTACCTGAGAGTGGTCATGAACCACTCATCACCTGCTCCTCTGGAGGCCCCAGAGGAGCTACATTGAAATAAAATCGCATTGCTAAAAAAAAAAAAAAAAAAA Translation:MKLTCVVIVAVLLLTACQLITADDSRGTQKHRSLRSKTKLSMSTGCMEAGSYCGSTTRI (SEQ IDNO:41) CCGFCAYFGKKCIDYPSN Toxin Sequence:Cys-Met-Xaa1-Ala-Gly-Ser-Xaa5-Cys-Gly-Ser-Thr-Thr-Arg-Ile-Cys-Cys-Gly-Phe-Cys-Ala-(SEQ ID NO:42)Xaa5-Phe-Gly-Lys-Lys-Cys-Ile-Asp-Xaa5-Xaa3-Ser-Asn-{circumflex over ( )}Name: Ay6.3 Species: aurisiacus Cloned: Yes DNA Sequence:ACCAAAACCATCATCAAAATGAAACTGACGTGTGTGGTGATCGTCGCCGTGCTGCT (SEQ ID NO:43)CCTGACGGCCTGTCAACTCATCACAGCTGATGACTCCAGAGGTACGCAGAAGCATCGTTCCCTGAGCTCGGCCACCAAACTCTCCATGTCGACTCGCTGCAAGGCTAAAGGAAAACCATGCAGTAGGATTGCGTATAACTGCTGCACCGGTTCTTGCAGATCAGGTAAATGTGGCTGATCCAGTGCCTGATCTTCCCCCTTCTGTGCTCTATCCTTTTCTGCCTGAGTCCTCCTTACCTGAGAGTGGTCATGAACCACTCATCACCTGCTCCTCTGGAGGCCCCAGAGGAGCTACATTGAAATAAAAGCCGCATTGC Translation:MKLTCVVIVAVLLLTACQLITADDSRGTQKHRSLSSATKLSMSTRCKAKGKPCSRIAYN (SEQ IDNO:44) CCTGSCRSGKCG Toxin Sequence:Cys-Lys-Ala-Lys-Gly-Lys-Xaa3-Cys-Ser-Arg-Ile-Ala-Xaa5-Asn-Cys-Cys-Thr-Gly-Ser-Cys-(SEQ ID NO:45) Arg-Ser-Gly-Lys-Cys-# Name: Ay6.4 Species: aurisiacusCloned: Yes DNA Sequence:ACCAAAACCATCATCAAAATGAAACTGACGTGTGTGGTGATCGTCGCCGTGCTGCT (SEQ ID NO:46)CCTGACGACCTGTCAACTCATCACAGCTGATGACTCCAGAGGTACGCAGGAGCATCGTGCCCTGAGGTCGAAGACAAAACTCTCCATGTTAACTTTGCGCTGCGCATCTTACGGAAAACCTTGTGGTATTGACAACGACTGCTGCAATGCATGCGATCCAGGAAGAAATATATGTACGTAGCTGATCCAGCGCCTGATCTTCCCCCTTCTGTGCTCTATCCTTTTCTGCCCGAGTCCTCCTTACCTGAGAGTGGTCATGAACCACTCATCACCTGCTCCCTGGAGGCCTCAGAGGAGCTACAATGAAATAAAAGCCGCATTGC Translation:MKLTCVVIVAVLLLTTCQLITADDSRGTQEHRALRSKTKLSMLTLRCASYGKPCGIDND (SEQ IDNO:47) CCNACDPGRNICT Toxin Sequence: Cys-Ala-Ser-Xaa5-Gly-Lys-Xaa3-Cys-Gly-Ile-Asp-Asn-Asp-Cys-Cys-Asn-Ala-Cys-Asp-Xaa3- (SEQ ID NO:48)Gly-Arg-Asn-Ile-Cys-Thr-{circumflex over ( )} Name: Bu6.1 Species:bullatus Cloned: Yes DNA Sequence:ACCAAAACCATCATCAAAATGAAACTGACGTGTGTGGCGATCGTCGCCGTGCTGCT (SEQ ID NO:49)CCTGACGGCCTGTCAGCTCATTACAGCTGAAGACTCCAGAGGTACGCATGAGCATCTTGCCCTGAAGTCGACCTCCAAAGTCTCCAAGTCGACTAGCTGCATGGAAGCCGGATCTTATTGCGGACCTGCTACTACGAAAATCTGCTGCGATTTTTGCAGTCCATTCAGCGATAGATGTATGAACAATCCCAACAATTGATCTTCCCCCTTGTGTGCTCCATCCTTTTCTGCCTGAGTCCTCCTTACCTGAGAGTGGTCATGAACCACTCATCACCTACTCCTCTGGAGGCTTCAGAGGAGCTACATTGAAATAAAAGCCGCATTGC Translation:MKLTCVAIVAVLLLTACQLITAEDSRGTHEHLALKSTSKVSKSTSCMEAGSYCGPATTK (SEQ IDNO:50) ICCDFCSPFSDRCMNNPNN Toxin Sequence:Ser-Thr-Ser-Cys-Met-Xaa1-Ala-Gly-Ser-Xaa5-Cys-Gly-Xaa3-A1a-Thr-Thr-Lys-Ile-Cys-Cys-(SEQ ID NO:51)Asp-Phe-Cys-Ser-Xaa3-Phe-Ser-Asp-Arg-Cys-Met-Asn-Asn-Xaa3-Asn-Asn-{circumflexover ( )} Name: Bu6.2 Species: bullatus Cloned: Yes DNA Sequence:ACCAAAACCATCATCAAAATGAAACTGACGTGTGTGGTGATCGTCGCCGTGCTGCT (SEQ ID NO:52)CCTGACGGCCTGTCAGCTCATTACAGCTGAAGACTCCAGAGGTACGCAGTTGCATCGTGCCCTGAGGAAGGCCACCAAACACCCTGTGTCGACTCGCTGCATTACTCCAGGAACACGATGTAAGGTTCCGAGCCAATGCTGCAGAGGTCCTTGCAAGAACGGTCGTTGTACTCCATCCCCTTCTGAATGGTAAATGTGGTTGATCCAGCGCCTGATCTTCCCCCTTCGTCGTGCTCCATCCTTTTCTGCCTGAGTCCTCCTTACCTGAGAGTGGTCATGAACCACTCATCACCTACTCCCCTGGAGGCTTCAGAGGAGCTACATTGAAATAAAAGCCGC ATTGCTranslation: MKLTCVVIVAVLLLTACQLITAEDSRGTQLHRALRKATKHPVSTRCITPGTRCKVPSQC(SEQ ID NO:53) CRGPCKNGRCTPSPSEW Toxin Sequence:Cys-Ile-Thr-Xaa3-Gly-Thr-Arg-Cys-Lys-Val-Xaa3-Ser-Gln-Cys-Cys-Arg-Gly-Xaa3-Cys-Lys-(SEQ ID NO:54)Asn-Gly-Arg-Cys-Thr-Xaa3-Ser-Xaa3-Ser-Xaa1-Xaa4-{circumflex over ( )}Name: Bu6.3 Species: bullatus Cloned: Yes DNA Sequence:ACCAAAACCATCATCAAAATGAAACTGACGTGTGTGGCGATCGTCGCCGTGCTGCT (SEQ ID NO:55)CCTGACGGCCTGTCAGCTCATTACAGCTGAGGACTCCAGAGATACGCAGAAGCATCGTGCCCTGAGGTCGGACACCAAACTCTCCATGTTGACTTTGCGCTGCGCAACTTACGGAAAACCTTGTGGTATTCAAAACGACTGCTGCAATACATGCGATCCAGCCAGAAGGACATGTACGTAGCTGATCCGGCGTCTTGATCCTCCGCTTCTGTGCTCCATCTTTTCTGCCTGAGTCCTCCTTACCTGAGAGTGGTCATGAACCACTCATCACCTACTCCTCTGGAGGCTTTAGAGGAGCTACATTGAAATAAAAGCCGCATTGC Translation:MKLTCVAIVAVLLLTACQLITAEDSRDTQKHRALRSDTKLSMLTLRCATYGKPCGIQND (SEQ IDNO:56) CCNTCDPARRTCT Toxin Sequence:Cys-Ala-Thr-Xaa5-Gly-Lys-Xaa3-Cys-Gly-Ile-Gln-Asn-Asp-Cys-Cys-Asn-Thr-Cys-Asp-Xaa3-(SEQ ID NO:57) Ala-Arg-Arg-Thr-Cys-Thr-{circumflex over ( )} Name: Bu6.4Species: bullatus Cloned: Yes DNA Sequence:ACCAAAACCATCATCAAAATGAAACTGACGTGTGTGGCGATCGTCGCCGTGCTGCT (SEQ ID NO:58)CCTGACGGCCTGTCAGCTCATTACAGCTGAAGACTCCAGAGGTACGCAGTTGCATCGTGCCCTGAGGAAGACCACCAAACTCTCCTTGTCGACTCGCTGCAAGGGTCCAGGAGCATCATGTATAAGGATTGCGTATAACTGCTGCAAGTATTCTTGCAGAAATGGTAAATGTGGCTGATCCAGCGCCTGATCTTCCCCCTTGTGTGCTCCATCCTTTTCTGCCTGAGTCCTCCTTACCTGAGAGTGGTCATGAACCACTCATCACCTACTCCTCTGGAGGCTTCAGAGGAGCTACATTGAAATAAAAGCCGCATTGC Translation:MKLTCVAIVAVLLLTACQLITAEDSRGTQLHRALRKTTKLSLSTRCKGPGASCIRIAYNC (SEQ IDNO:59) CKYSCRNGKCG Toxin Sequence:Cys-Lys-Gly-Xaa3-Gly-Ala-Ser-Cys-Ile-Arg-Ile-Ala-Xaa5-Asn-Cys-Cys-Lys-Xaa5-Ser-Cys-(SEQ ID NO:60) Arg-Asn-Gly-Lys-Cys-# Name: Bu6.5 Species: bullatusCloned: Yes DNA Sequence:ATCAAAACCATCATCAAAATGAAACTGACGTGTGTGGTGATCGTCGCCGTGCTGCTC (SEQ ID NO:61)CTGACGGCCTGTCAGCTCATTACAGCTGAAGACTCCAGAGGTACGCATGAGCATCTTGCCCTGAAGTCGACCTCCAAAGTCTCCAAGTCGACTAGCTGCATGGCAGCCGGATCTTATTGCGGACCTGCTACTACGAATATCTGCTGCGATTTTTGCAGTCCATTCAGCGATAGATGTATGAAAAAGCCCAACAATTGATCTTCCCCCTTCTGTGCTCTATCCTTTTCTGCCTGAGTCCTCCTTACCTGAGAGTGGTCATGAACCACTCATCACCTACTCCTCTGGAGGCTTCAGAGGAGCTACATTGAAATAAAAGCCGCATTGC Translation:MKLTCVVIVAVLLLTACQLITAEDSRGTHEHLALKSTSKVSKSTSCMAAGSYCGPATTN (SEQ IDNO:62) ICCDFCSPFSDRCMKKPNN Toxin Sequence:Ser-Thr-Ser-Cys-Met-Ala-Ala-Gly-Ser-Xaa5-Cys-Gly-Xaa3-Ala-Thr-Thr-Asn-Ile-Cys-Cys-(SEQ ID NO:63)Asp-Phe-Cys-Ser-Xaa3-Phe-Ser-Asp-Arg-Cys-Met-Lys-Lys-Xaa3-Asn-Asn-{circumflexover ( )} Name: Bu6.6 Species: bullatus Cloned: Yes DNA Sequence:ACCAAAACCATCATCAAAATGAAACTGACGTGTGTGGTGATCGTCGCCGTGCTGCT (SEQ ID NO:64)CCTGACGGCCTGTCAGCTCATTATAGCTGAGGACTCCAGAGGTACGCAGTTGCATCGTGCCCTGAGGAAGGCCACCAAACTCTCCGTGTCGACTCGCTGCAAGAGTAAAGGATCATCATGTCATAGGACTTCGTATGACTGCTGCACGGGTTCTTGCAGAAATGGTAGATGTGGCTGATCCAGCGCCTGATCTTCCCCCTTCTGTGCTCCATCCTTTTCTGCCTGAGTCCTCCTTACCTGAGAGTGGTCATGAACCACTCATCACCTACTCCTCTGGAGGCTTCAGAGGAGCTACATTGAAATAAAAGCCGCATTGC Translation:MKLTCVVIVAVLLLTACQLIIAEDSRGTQLHRALRKATKLSVSTRCKSKGSSCHRTSYD (SEQ IDNO:65) CCTGSCRNGRCG Toxin Sequence:Cys-Lys-Ser-Lys-Gly-Ser-Ser-Cys-His-Arg-Thr-Ser-Xaa5-Asp-Cys-Cys-Thr-Gly-Ser-Cys-Arg-(SEQ ID NO:66) Asn-Gly-Arg-Cys-# Name: Ca6.4 Species: caracteristicusCloned: Yes DNA Sequence:GGATCCATGAAACTGACGTGCGTGGTGATCATCGCCGTGCTGTTCCTGACGGCCTGT (SEQ ID NO:67)CAACTCATTACAGGTGAGCAGAAGGACCATGCTCTGAGGTCAACTGACAAAAACTCCAAGTTGACTAGGCAGTGCTCGGCTAACGGTGGATCTTGTACTCGTCATTTTCACTGCTGCAGCCTCTATTGCAATAAAGATTCCAGTGTATGTGTGGCAACCTCATACCCGTGAGTGGCCATGAACCCCTCAATACCCTCTCCTCTGGAGGCTTCAGAGGAACTGCATTGAAATAAAACCGCATTACAAAAAAAAAAAAAAAAAAAA Translation:MKLTCVVIIAVLFLTACQLITGEQKDHALRSTDKNSKLTRQCSANGGSCTRHFHCCSLY (SEQ IDNO:68) CNKDSSVCVATSYP Toxin Sequence:Xaa2-Cys-Ser-Ala-Asn-Gly-Gly-Ser-Cys-Thr-Arg-His-Phe-His-Cys-Cys-Ser-Leu-Xaa5-Cys-(SEQ ID NO:69)Asn-Lys-Asp-Ser-Ser-Val-Cys-Val-Ala-Thr-Ser-Xaa5-Xaa3-{circumflex over( )} Name: C6.1 Species: catus Cloned: Yes DNA Sequence: Translation:CKSTGASCRRTSYDCCTGSCRSGRCG (SEQ ID NO:70) Toxin Sequence:Cys-Lys-Ser-Thr-Gly-Ala-Ser-Cys-Arg-Arg-Thr-Ser-Xaa5-Asp-Cys-Cys-Thr-Gly-Ser-Cys-Arg-(SEQ ID NO:71) Ser-Gly-Arg-Cys-# Name: C6.4 Species: catus Cloned: YesDNA Sequence: TCGACTCGCTGCCAGGGTAGAGGAGCATCATGTCGTAAGACTATGTATAACTGCTG(SEQ ID NO:72) CAGCGGTTCTTGCAACAGAGGTAGTTGTGGCTGATCCGGCGCCTGATCTTCCCCCTTCCGTGCTCTATCCTTTTCTGCCTGATTCCTCCTTACCTGAGAGCGGTCATGAACCACTCATCACCTGCTCCTCTGGAGGCCTCAGAGGAGCTACATTGAAATAAAAGCCGCATT GC Translation:STRCQGRGASCRKTMYNCCSGSCNRGSCG (SEQ ID NO:73) Toxin Sequence:Cys-Gln-Gly-Arg-Gly-Ala-Ser-Cys-Arg-Lys-Thr-Met-Xaa5-Asn-Cys-Cys-Ser-Gly-Ser-Cys-(SEQ ID NO:74) Asn-Arg-Gly-Ser-Cys-# Name: C6.5 Species: catus Cloned:Yes DNA Sequence:TCGACACGCTGCTTGCCTGCCGGAGAGTCTTGCCTTTTTAGTAGGATTAGATGCTGC (SEQ ID NO:75)GGTACTTGCAGTTCAGTCTTAAAGTCATGTGTGAGCTGATCCAGCTGCTGATCTTCCTCCTCCTGTGCTCCATCCTTTTCTGCCTGAGTCCTCCTTATCTGAGAGTGGTCATGAACCACTCACCACCTACTCTTCTGGAGGCTTCAGAGGAGCTACAGTGAAATAAAAGCC GCATTGCTranslation: STRCLPAGESCLFSRIRCCGTCSSVLKSCVS (SEQ ID NO:76) ToxinSequence:Cys-Leu-Xaa3-Ala-Gly-Xaa1-Ser-Cys-Leu-Phe-Ser-Arg-Ile-Arg-Cys-Cys-Gly-Thr-Cys-Ser-(SEQ ID NO:77) Ser-Val-Leu-Lys-Ser-Cys-Val-Ser-{circumflex over ( )}Name: C6.6 Species: catus Cloned: Yes DNA Sequence:TCGACACGCTGCCAGGGTAGAGGAGGACCATGTACTAAGGCTGTGTTTAACTGCTG (SEQ ID NO:78)CAGCGGTTCTTGCAACAGAGGTAGATGTGGCTGATCCAGCGCCTGATCTTCCCCCTTCTGTGCTCTATCCTTTTCTGCCTGAGTCCTCCTTACTGAGAGTAGTCATGAACCACTCATCACCTACTCCTCTGGAGGCCTCAGAGAGCTACATTGAAATAAAAGCCGCATTGC Translation:STRCQGRGGPCTKAVFNCCSGSCNRGRCG (SEQ ID NO:79) Toxin Sequence:Cys-Gln-Gly-Arg-Gly-Gly-Xaa3-Cys-Thr-Lys-Ala-Val-Phe-Asn-Cys-Cys-Ser-Gly-Ser-Cys-(SEQ ID NO:80) Asn-Arg-Gly-Arg-Cys-# Name: C6.7 Species: catus Cloned:Yes DNA Sequence:TTAACTTTGCGCTGCGCAACTTACGGAAAACCTTGTGGTATTCAAAACGACTGCTGC (SEQ ID NO:81)AATACATGCGATCCAGCCAGAAAGACATGTACGTAGCTGATCCGGCGTCTGATCTCCCCCCTTCTGTGCTCTATCCTTTTCTGCCTGAGTCCTCCTTACCTGAGAGTGGTCATGAACCACTCATCACCTGCTCCTCTGGAGGCCTCGGGGGAGCTACATTGAAATAAAAG CCGCATTGCTranslation: LTLRCATYGKPCGIQNDCCNTCDPARKTCT (SEQ ID NO:82) ToxinSequence:Cys-Ala-Thr-Xaa5-Gly-Lys-Xaa3-Cys-Gly-Ile-Gln-Asn-Asp-Cys-Cys-Asn-Thr-Cys-Asp-Xaa3-(SEQ ID NO:83) Ala-Arg-Lys-Thr-Cys-Thr-{circumflex over ( )} Name: C6.8Species: catus Cloned: Yes DNA Sequence:TCGACTCGCTGCCGGGGTAGAGGAGGACCATGTACTAAGGCTATGTTTAACTGCTG (SEQ ID NO:84)CAGCGGTTCTTGCAACAGAGGTAGATGTGGCTGATCCAGCGCCTGATCTTCCCCCTTCTGTGCTCTATCCTTTTCTGCCTGAGTCCTCCTTAACTGAGAGTAGTCATGAACCACTCATCACCTACTCCTCTGGAGGCCTCAGAGAAGCATCATTGAAATAAAAGCCGCATT GC Translation:STRCRGRGGPCTKAMFNCCSGSCNRGRCG (SEQ ID NO:85) Toxin Sequence:Cys-Arg-Gly-Arg-Gly-Gly-Xaa3-Cys-Thr-Lys-Ala-Met-Phe-Asn-Cys-Cys-Ser-Gly-Ser-Cys-(SEQ ID NO:86) Asn-Arg-Gly-Arg-Cys-# Name: Cr6.1 Species: circumcisusCloned: Yes DNA Sequence:ACCAAAACCATCATCAAAATGAAACTGACGTGTGTGGTGATCGTCGCCGTGCTGCT (SEQ ID NO:87)CCTGACGACCTGTCAACTCATCACAGCTGATGACTCCAGAGGTACGCAGGAGCATCGTGCCCTGAGGTCGGACACCAAACTCCCCATGTCGACTCGCTGCAAGGGTAAAGGAGCATCATGTCGTAAGACTATGTATAACTGCTGCAGCGGTTCTTGCAGCAACGGTAGATGTGGCTGATCCAGCGCCTGATCTTCCCCCTTCTGCTGCTCTATCCTTTTCTGCCTGAGTCCTCCTTACCTGAGAGCTGGTCATGAACCACTCATCACCTGCTCCTCTGGAGGCCCAGAGGAGCTACATTGAAATAAAAGCCGCATTGC Translation:MKLTCVVIVAVLLLTTCQLITADDSRGTQEHRALRSDTKLPMSTRCKGKGASCRKTMY (SEQ IDNO:88) NCCSGSCSNGRCG Toxin Sequence:Cys-Lys-Gly-Lys-Gly-Ala-Ser-Cys-Arg-Lys-Thr-Met-Xaa5-Asn-Cys-Cys-Ser-Gly-Ser-Cys-Ser-(SEQ ID NO:89) Asn-Gly-Arg-Cys-# Name: Cr6.2 Species: circumeisusCloned: Yes DNA Sequence:ACCAAAACCATCATCAAAATGAAACTGACGTGTGTGGTGATCGTCGCCGTGCTGCT (SEQ ID NO:90)CCTGACGACCTGTCAACTCATCACAGCTGATGACTCCAGAGGTACGCAGAAGCATCGTGCCCTGAGGTCGGCCACCAAAGTCTCCAAGTCGACTAGCTGCATGGAAGCCGGATCTTATTGCCGCTCTACTACGAGAACCTGCTGCGGTTATTGCTCTTATTTCAGCAAAAAATGTATTGACTTTCCCAGCAACTGATCTTCCCCCTACTGTGCTCTATCCTTTTCTGCCTGAGTCCTCCTTACCTGAGAGTGGTCATGAACCACTCATCACCCTACTCCTCTGGAGGCCCAGAGGAGCTACATTGAAATAAAAGCCGCATTGC Translation:MKLTCVVIVAVLLLTTCQLITADDSRGTQKHRALRSATKVSKSTSCMEAGSYCRSTTRT (SEQ IDNO:91) CCGYCSYFSKKCIDFPSN Toxin Sequence:Ser-Thr-Ser-Cys-Met-Xaa1-Ala-Gly-Ser-Xaa5-Cys-Arg-Ser-Thr-Thr-Arg-Thr-Cys-Cys-Gly-(SEQ ID NO:92)Xaa5-Cys-Ser-Xaa5-Phe-Ser-Lys-Lys-Cys-Ile-Asp-Phe-Xaa3-Ser-Asn-{circumflexover ( )} Name: Cr6.3 Species: circumcisus Cloned: Yes DNA Sequence:ACCAAAACCATCATCAAAATGAAACTGACGTGTGTGGTGATCGTCGCCGTGCTGCT (SEQ ID NO:93)CCTGACGACCTGTCAACTCATCACAGCTGATGACTCCAGAGGTACGCAGGAGCATCGTGCCCTGAGGTCGGACACCAAACTCCCCATGTCGACTCGCTGCAAGAGTAAAGGAGCAAAATGTTCAAGGCTTATGTATGACTGCTGCAGCGGTTCTTGCAGCAGGTACTCAGGTAGATGTGGCTGATCCAGCGCCTGATCTTCCCCCTTCTGCTGCTCTATCCTTTTCTGCCTGAGTCCTCCTTACCTGAGAGTGGTCATGAACCACTCATCACCTACTCCTCTGGAGGCCCAGAGGAGCTACATTGAAATAAAAGCCGCATTGC Translation:MKLTCVVIVAVLLLTTCQLITADDSRGTQEHRALRSDTKLPMSTRCKSKGAKCSRLMY (SEQ IDNO:94) DCCSGSCSRYSGRCG Toxin Sequence:Cys-Lys-Ser-Lys-Gly-Ala-Lys-Cys-Ser-Arg-Leu-Met-Xaa5-Asp-Cys-Cys-Ser-Gly-Ser-Cys-Ser-(SEQ ID NO:95) Arg-Xaa5-Ser-Gly-Arg-Cys-# Name: Cr6.4 Species:circumcisus Cloned: Yes DNA Sequence:ACCAAAACCATCATCAAAATGAAACTGACGTGTGTGGTGATCGTCGCCGTGCTGCT (SEQ ID NO:96)CCTGACGACCTGTCAACTCATCACAGCTGATGACTCCAGAGGTACGCAGAAGCATCGTTCCCTGACGTCGGCCACCAAAGTCTCCAAGTCGACTGGCTGCATGAAAGCCGGATCTTATTGCCGCTCTACTACGAGAACTTGCTGCGGTTATTGCGCTTATTTCGGCAAAAAATGTATTGACTATCCCAGCAACTGATCTTCCCCCTACTGTGCTCTATCCTTTTCTGCCTAAGTCCTCCTTACCTGAGAGTGGTCATGAACCACTCATCACCCTACTCCTCTGGAGGCCCAGAGGAGCTACATTGAAATAAAAGCCGCATTGC Translation:MKLTCVVIVAVLLLTTCQLITADDSRGTQKHRSLTSATKVSKSTGCMKAGSYCRSTTRT (SEQ IDNO:97) CCGYCAYFGKKCIDYPSN Toxin Sequence:Ser-Thr-Gly-Cys-Met-Lys-Ala-Gly-Ser-Xaa5-Cys-Arg-Ser-Thr-Thr-Arg-Thr-Cys-Cys-Gly-(SEQ ID NO:98)Xaa5-Cys-Ala-Xaa5-Phe-Gly-Lys-Lys-Cys-Ile-Asp-Xaa5-Xaa3-Ser-Asn-{circumflexover ( )} Name: Cn6.1 Species: consors Cloned: Yes DNA Sequence:ATGAAACTGACGTGTGTGGTGATCGTCGCCGTGCTGCTCCTGACGGCCTGTCAACTC (SEQ ID NO:99)CTCACAGCTGATGACTCCAGAGGTACGCAGAAGCATCGTGCCCTGAAGTCTTACACCAAACTCTCCATGTTAACTTTGCGCTGCGCATCTTACGGAAAACCTTGTGGTATTGACAACGACTGCTGCAATACATGCGATCCAGCCAGAAAGACATGTACGTAGCTGATCCGGCGTCTGATCTTCCCCCTTCTGTGCTCTATCCTTTTCTGCCTGAGTCCTCCTTACCTGAGAGTGGTCATGAACCACTCATCACCTAGCTCCTCTGGAGGCTTCAGAGGAGCTACAATGAAATAAAAGCGCATTGC Translation:MKLTCVVIVAVLLLTACQLLTADDSRGTQKHRALKSYTKLSMLTLRCASYGKPCGIDN (SEQ IDNO:100) DCCNTCDPARKTCT Toxin Sequence:Cys-Ala-Ser-Xaa5-Gly-Lys-Xaa3-Cys-Gly-Ile-Asp-Asn-Asp-Cys-Cys-Asn-Thr-Cys-Asp-Xaa3-(SEQ ID NO:101) Ala-Arg-Lys-Thr-Cys-Thr-{circumflex over ( )} Name:Cn6.2 Species: consors Cloned: Yes DNA Sequence:ATGAAACTGACGTGTGTGGTGATCGTCGCCGTGCTGCTCCTGACGGCCTGTCAACTC (SEQ IDNO:102) CTCACAGCTGATGACTCCAGAGGTACGCAGAAGCATCGTGCCCTGAGGTCGGACACCAAACTCTCCATGTCGACTCGCTGCAAGGGTACAGGAAAACCATGCAGTAGGATTGCGTATAACTGCTGCACCGGTTCTTGCAGATCAGGTAAATGTGGCTGATCCAGCGCCT GATCTCCCCCCTranslation: MKLTCVVIVAVLLLTACQLLTADDSRGTQKHRALRSDTKLSMSTRCKGTGKPCSRIAY(SEQ ID NO:103) NCCTGSCRSGKCG Toxin Sequence:Cys-Lys-Gly-Thr-Gly-Lys-Xaa3-Cys-Ser-Arg-Ile-Ala-Xaa5-Asn-Cys-Cys-Thr-Gly-Ser-Cys-(SEQ ID NO:104) Arg-Ser-Gly-Lys-Cys-# Name: Cn6.3 Species: consorsCloned: Yes DNA Sequence:ATGAAACTGACGTGTGTGGTGATCGTCGCCGTGCTGCTCCTGACGGCCTGTCAACTC (SEQ IDNO:105) ATCACAGCTGATGACTCCAAAGGTACGCAGAAGCATCGTTCCCTGAGGTCGACCACCAAAGTCTCCAAGGCGACTGACTGCATTGAAGCCGGAAATTATTGCGGACCTACTGTTATGAAAATCTGCTGCGGCTTTTGCAGTCCATACAGCAAAATATGTATGAACTATCCCCAAAATTGATCTTCCCCCTTCTGTGCTCTATCCTTTTCTGCCTGAGTCCTCCTTACCTGAGAGTGGTCATGAACCACTCATCACCTCGTCCC Translation:MKLTCVVIVAVLLLTACQLITADDSKGTQKHRSLRSTTKVSKATDCIEAGNYCGPTVM (SEQ IDNO:106) KICCGFCSPYSKICMNYPQN Toxin Sequence:Ala-Thr-Asp-Cys-Ile-Xaa1-Ala-Gly-Asn-Xaa5-Cys-Gly-Xaa3-Thr-Val-Met-Lys-Ile-Cys-Cys-(SEQ ID NO:107)Gly-Phe-Cys-Ser-Xaa3-Xaa5-Ser-Lys-Ile-Cys-Met-Asn-Xaa5-Xaa3-Gln-Asn-{circumflexover ( )} Name: Cn6.4 Species: consors Cloned: Yes DNA Sequence:ATGAAACTGACGTGTGTGGTGATCGTCGCCGTGCTGCTCCTGACGGCCTGTCAACTC (SEQ IDNO:108) CTCACAGCTGATGACTCCAGAGGTACGCAGAAGCATCGTGCCCTGAGGTCGGACACCAAACTCTCCATGTCGACTCGCTGCAAAGGTAAAGGAGCATCATGTACAAGGCTTATGTATGACTGCTGCCACGGTTCTTGCAGCAGCAGCAAGGGTAGATGTGGCTGATCCGGCGCCTGATCTTCCCCCTTCTGTGCTCTATCCTTTTCTGCCTGAGTCCTCCTTACCTGAGAGGTGGTCATGAACCACTCATCACCTGCTCCCCTG Translation:MKLTCVVIVAVLLLTACQLLTADDSRGTQKHRALRSDTKLSMSTRCKGKGASCTRLM (SEQ ID NO:19)YDCCHGSCSSSKGRCG Toxin Sequence:Cys-Lys-Gly-Lys-Gly-Ala-Ser-Cys-Thr-Arg-Leu-Met-Xaa5-Asp-Cys-Cys-His-Gly-Ser-Cys-(SEQ ID NO:110) Ser-Ser-Ser-Lys-Gly-Arg-Cys-# Name: Cn6.5 Species:consors Cloned: Yes DNA Sequence:GGATCCATGAAACTGACGTGCATGGTGATCGTCGCCGTGCTGCTCCTGACGGCCTGT (SEQ IDNO:111) CAACTCATCACAGCTGATGACTCCAGAGGTACGCAGAAGCATCGTGCCCTGAGGTCGGACACCAAACTCTCCATGTCAACTCGCTGCAAGGGTAAAGGAGCATCATGTCATAGGACTTCGTATGACTGCTGCACCGGTTCTTGCAACAGAGGTAAATGTGGCTGATCCGGCGCCTGATCTTCCCCCTTCTGTGCTCTATCCTTTTCTGCCTGAGTCATCCATACCTG TGCTCGAGTranslation: MKLTCMVIVAVLLLTACQLITADDSRGTQKHRALRSDTKLSMSTRCKGKGASCHRTSY(SEQ ID NO:112) DCCTGSCNRGKCG Toxin Sequence:Cys-Lys-Gly-Lys-Gly-Ala-Ser-Cys-His-Arg-Thr-Ser-Xaa5-Asp-Cys-Cys-Thr-Gly-Ser-Cys-Asn-(SEQ ID NO:113) Arg-Gly-Lys-Cys-# Name: Cn6.6 Species: consors Cloned:Yes DNA Sequence:GGATCCATGAAACTGACGTGCGTGGTGATCGTCGCCGTGCTGCTCCTGACGGCCTGT (SEQ IDNO:114) CAACTCATCACAGCTGATGACTCCAGAGGTACGCAGAAGCATCGTGCCCTGAAGTCGGACACCAAACTCTCCATGTTAACTTTGCGCTGCGCATCTTACGGAAAACCTTGTGGTATTTACAACGACTGCTGCAATACATGCGATCCAGCCAGAAAGACATGTACGTAGCTGATCCGGCGTCTGATCTTCCCCCTTCTGTGCTCTATCCTTTTCTGCCTGAGTCATCCATACCTGTGCTCGAG Translation:MKLTCVVIVAVLLLTACQLITADDSRGTQKHRALKSDTKLSMLTLRCASYGKPCGIYN (SEQ IDNO:115) DCCNTCDPARKTCT Toxin Sequence:Cys-Ala-Ser-Xaa5-Gly-Lys-Xaa3-Cys-Gly-Ile-Xaa5-Asn-Asp-Cys-Cys-Asn-Thr-Cys-Asp-(SEQ ID NO:116) Xaa3-Ala-Arg-Lys-Thr-Cys-Thr-{circumflex over ( )} Name:Cn6.7 Species: consors Cloned: Yes DNA Sequence:GGATCCATGAAACTGACGTGTGTGGTGATCGTCGCCGTGCTGCTCCTGACGGCCTGT (SEQ IDNO:117) CAACTCATCACAGCTGATGACTCCAGAGGTACGCAGAAGCATCGTGCCCTGAGGTCGGACACCAAACTCTCCATGTCGACTCGCTGCAAGGGTACAGGAAAACCATGCAGTAGGGTTGCGTATAACTGCTGCACCGGTTCTTGCAGATCAGGTAAATGTGGCTGATCCAGTGCCTGATCTTCCCCCTTCTGTGCTCTATCCTTTTCTGCCTGAGTCCTCCTTACCTGAGAGTGGTCATGAACCACTCATCACCTGCTCCTCTGGAGGCTTCAGAGGAGCTACATTGAAATAAAAGCCGCATTGCANTGNANAAAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGGAAAAAAAAAAAAAAAAAAAA Translation:MKLTCVVIVAVLLLTACQLITADDSRGTQKHRALRSDTKLSMSTRCKGTGKPCSRVAY (SEQ IDNO:118) NCCTGSCRSGKCG Toxin Sequence:Cys-Lys-Gly-Thr-Gly-Lys-Xaa3-Cys-Ser-Arg-Val-Ala-Xaa5-Asn-Cys-Cys-Thr-Gly-Ser-Cys-(SEQ ID NO:119) Arg-Ser-Gly-Lys-Cys-# Name: Cn6.8 Species: consorsCloned: Yes DNA Sequence:GGATCCATGAAACTGACGTGCATGGTGATCGTCGCCGTGCTGCTCCTGACGGCCTGT (SEQ IDNO:120) CAACTCATCACAGCTGATGACTCCAGAGGTACGCAGAAGCATCGTTCCCTGAGGTCGACCACCAAAGTCTCCAAGTCGACTAGCTGCATGAAAGCCGGGTCTTATTGCCGCTCTACTACGAGAACCTGCTGCGGTTATTGCGCTTATTTCGGCAAATTTTGTATTGACTTTCCCAGCAACTGATCTTCCCCCTACTGTGCTCTATCCTTTTCTGCCTCTGCCTGAGTCCTCCTTACCTGAGAGTGGTCATGAACCACTCATCACCTGCTCCCCTGGAGGCCTCAGAGGAGCTACAATGAAATAAAAGCCGCATTGCAAAAAAAAAAAAAAAAAAAA Translation:MKLTCMVIVAVLLLTACQLITADDSRGTQKHRSLRSTTKVSKSTSCMKAGSYCRSTTRT (SEQ IDNO:121) CCGYCAYFGKFCIDFPSN Toxin Sequence:Ser-Thr-Ser-Cys-Met-Lys-Als-Gly-Ser-Xaa5-Cys-Arg-Ser-Thr-Thr-Arg-Thr-Cys-Cys-Gly-(SEQ ID NO:122)Xaa5-Cys-Ala-Xaa5-Phe-Gly-Lys-Phe-Cys-Ile-Asp-Phe-Xaa3-Ser-Asn-{circumflexover ( )} Name: Da6.8 Species: dalli Cloned: Yes DNA Sequence:ACCAAAACCATCATCAAAATGAAACTGACGTGTGTGGTGATCGTCGCCGTGCTGTTC (SEQ IDNO:123) CTGACGGCCTGTCAACTCATCACAGCTGATGACTCCAGAAGTACGCAGAAGCATCGTGCTCTGAGGTCGACCATCAAACACTCCATGTTGACTAGGAGCTGCACGCCTCCCGGAGGACCTTGTGGTTATTATAATGACTGCTGCAGTCATCAATGCAATATAAGCAGAAATAAATGCGAGTAGCTGATCCGGCATCTGATCTTCCCCTTCTGTGCTCGTCCTAACCTGAGAGTGGTCATGAACCATCATCACCTACTCCTCTGGAGGCTTCAGAGGAGCTACATGGAAATAAAAGCCGCATTGC Translation:MRLTCVVIVAVLFLTACQLITADDSRSTQKHRALRSTIKHSMLTRSCTPPGGPCGYYND (SEQ IDNO:124) CCSHQCNISRNKCE Toxin Sequence:Ser-Cys-Thr-Xaa3-Xaa3-Gly-Gly-Xaa3-Cys-Gly-Xaa5-Xaa5-Asn-Asp-Cys-Cys-Ser-His-Gln-(SEQ ID NO:125) Cys-Asn-Ile-Ser-Arg-Asn-Lys-Cys-Xaa1-{circumflex over( )} Name: Di6.1 Species: distans Cloned: Yes DNA Sequence:ACCAAAACCATCATCAAAATGAAACTGACGTGCGTGTTGATCATCGCCGTGCTGTTC (SEQ IDNO:126) CTGACGGCCTGTCAACTCACTAGAGGAAAGCTGGAGCGTCCTGTTCTGAGGTCGAGCGACCAAACCTCCGGGTCAACGAAGAGATGCGAAGATCCTGGTGAACCTTGCGGAAGTGATCATTCCTGCTGCGGCGGTAGTTGCAACCACAACGTCTGCGCCTGAAGCTGGTCTGGCATCTGACCATTCCCCTTCTGTACTCTATCTCTATTGCCTGAGTCATCTTTACCTGTGAGTGGTCATGAATCTCTCAATACCTTCTCCCCTGGAGGCTTCAGAAGAACTAG ATTGAAATATranslation:MKLTCVLIIAVLFLTACQLTRGKLERPVLRSSDQTSGSTKRCEDPGEPCGSDHSCCGGSC (SEQ IDNO:127) NHNVCA Toxin Sequence:Cys-Xaa1-Asp-Xaa3-Gly-Xaa1-Xaa3-Cys-Gly-Ser-Asp-His-Ser-Cys-Cys-Gly-Gly-Ser-Cys-(SEQ ID NO:128) Asn-His-Asn-Val-Cys-Ala-{circumflex over ( )} Name: E6.2Species: ermineus Cloned: Yes DNA Sequence:ATGAAACTGACGTGTGTGGTGATCGTCGCCGTGCTGCTCCTGACGGCCTGTCAACTC (SEQ IDNO:129) ATCACAGCTGACGACTCCAGACGTACGCAGAAGCATCGTGCCCTGAGGTCGACCACCAAACGCGCCACGTCGAATCGCCCCTGCAAGCCGAAAGGACGAAAATGTTTTCCGCATCAGAAGGACTGCTGCAATAAAACGTGCACCAGATCAAAATGTCCCTGATCTTCCCCCTTCTGTGCTGTATCCTTTTCTGCCTGAGTCCTCCTTACCTGAGAGTGGTCAGTAACCACTCATCACCATCTCCTCTGGAGG Translation:MKLTCVVIVAVLLLTACQLITADDSRRTQKHRALRSTTKRATSNRPCKPKGRKCFPHQK (SEQ IDNO:130) DCCNKTCTRSKCP Toxin Sequence:Xaa3-Cys-Lys-Xaa3-Lys-Gly-Arg-Lys-Cys-Phe-Xaa3-His-Gln-Lys-Asp-Cys-Cys-Asn-Lys-Thr-(SEQ ID NO:131) Cys-Thr-Arg-Ser-Lys-Cys-Xaa3-{circumflex over ( )} Name:E6.3 Species: ermineus Cloned: Yes DNA Sequence:AACTCATCACAGCTGATGACTCCAGAGGTACGCAGAACGATCGTGCCCTGAGGTCG (SEQ ID NO:132)ACCACCAAACTCTCCATGCTGACTCGGGCCTGCTGGTCTTCCGGAACACCTTGTGGTACTGATAGTTTATGCTGCGGTGGATGCAATGTATCCAAAAGTAAATGTAACTAGCTGATTCGGCGTCTGAACTTCCCCCTTCTGTGCTCTATCCTTTTCTGCCCGAGTCCTCCATACCTGAGAATGGTCATGAACCACTCATCACCTACTCCTCTGGAGACCTCAGAAGAGCTACACTGAAATAAAAGCGCTTGC Translation:LITADDSRGTQNDRALRSTTKLSMLTRACWSSGTPCGTDSLCCGGCNVSKSKCN (SEQ ID NO:133)Toxin Sequence:Ala-Cys-Xaa4-Ser-Ser-Gly-Thr-Xaa3-Cys-Gly-Thr-Asp-Ser-Leu-Cys-Cys-Gly-Gly-Cys-Asn-(SEQ ID NO:134) Val-Ser-Lys-Ser-Lys-Cys-Asn-{circumflex over ( )} Name:G6.1 Species: geographus Cloned: Yes DNA Sequence:GGATCCATGAAACTGACGTGCGTGGTGATCGTCGCCGTGCTGCTCCTGACGGCCTGT (SEQ IDNO:135) CAACTCATCACAGCTGATGACTCCAGAGGTACGCAGAAGCATCGTGCCCTGGGGTCGACCACCGAACTCTCCTTGTCGACTCGCTGCAAGTCACCCGGATCTTCATGTTCACCGACTAGTTATAATTGCTGCAGGTCTTGCAATCCATACGCCAAAAGATGTTACGGCTAATCCAGCGCCTGATCTTCCCCCTTCTGTGCTCTATCCCTTCCTGTCTGAGTCCTCCTTACCTGAGAGTGGTCATGAACCACTCCTCACCTACTTCTCTGGAGGCTTCGGAGGAGCTACATTGAAATAAAAGCCGCATTGTAAAAAAAAAAAAAAAAAA Translation:MKLTCVVIVAVLLLTACQLITADDSRGTQKHRALGSTTELSLSTRCKSPGSSCSPTSYNC (SEQ IDNO:136) CRSCNPYAKRCYG Toxin Sequence:Cys-Lys-Ser-Xaa3-Gly-Ser-Ser-Cys-Ser-Xaa3-Thr-Ser-Xaa5-Asn-Cys-Cys-Arg-Ser-Cys-Asn-(SEQ ID NO:137) Xaa3-Xaa5-Ala-Lys-Arg-Cys-Xaa5-# Name: G6.2 Species:geographus Cloned: Yes DNA Sequence:GGATCCATGAAACTGACGTGTGTGGTGATCGTCGCCGTGCTGCTCCTGACGGCCTGT (SEQ IDNO:138) CAACTCATCACAGCTGATGACTCCAGAGGTACGCAGAAGCATCGTGCCCTGAGGTCGTCCACCAAACTCACCTTGTCGACTCGCTGCAAATCACCCGGAACTCCATGTTCAAGGGGTATGCGTGATTGCTGCACGCCTTGCTTGTTATACAGCAACAAATGTAGGCGCTACTAACCCAGCGCCTGATCTTCCCCCTTCTGTGCTCTATTCCTTTCTGCCTGAGTCCTCCTTACCTGAAAGTGGTCATGAACCACTCATCACCTACTTCTCTGGAGGCTTCAGAAGAGCTACATTGAAATAAAAGCCGCATTGCAATGACAAAAAAAAAAAAAAAAAAAA Translation:MKLTCVVIVAVLLLTACQLITADDSRGTQKHRALRSSTKLTLSTRCKSPGTPCSRGMRD (SEQ IDNO:139) CCTPCLLYSNKCRRY Toxin Sequence:Cys-Lys-Ser-Xaa3-Gly-Thr-Xaa3-Cys-Ser-Arg-Gly-Met-Arg-Asp-Cys-Cys-Thr-Xaa3-Cys-Leu-(SEQ ID NO:140) Leu-Xaa5-Ser-Asn-Lys-Cys-Arg-Arg-Xaa5-{circumflex over( )} Name: w-GVIA Species: geographus Cloned: Yes DNA Sequence:GGAATTCCGTTTCTGCGCTGCTTCCTTTGGCATCACCAAAACCATCATCAAAATGAA (SEQ IDNO:141) ACTGACGTGTGTGGTGATCGTCGCCGTGCTGCTCCTGACGGCCTGTCAACTCATCACAGCTGATGACTCCAGAGGTACGCAGAAGCATCGTGCCCTGGGGTCGACCACCGAACTCTCCTTGTCGACTCGCTGCAAGTCACCCGGATCTTCATGTTCACCGACTAGTTATAATTGCTGCAGGTCTTGCAATCCATACACCAAAAGATGTTACGGCTAATCCAGCGCCTGATCTTCCCTGCTCTGAGTCCTCCTTACCTGAGAGTGGTCATGAACCACTCATCACCTACTTCTCTAGGCGGTTCGGAGGAGCTACATTGAAATAAAAGCCGCATTGCAAAAA AAAAAAAAAATranslation:MKLTCVVIVAVLLLTACQLITADDSRGTQKHRALGSTTELSLSTRCKSPGSSCSPTSYNC (SEQ IDNO:142) CRSCNPYTKRCYG Toxin Sequence:Cys-Lys-Ser-Xaa3-Gly-Ser-Ser-Cys-Ser-Xaa3-Thr-Ser-Xaa5-Asn-Cys-Cys-Arg-Ser-Cys-Asn-(SEQ ID NO:143) Xaa3-Xaa5-Thr-Lys-Arg-Cys-Xaa5-# Name: w-GVIB Species:geographus Isolated: Yes Toxin Sequence:Cys-Lys-Ser-Xaa3-Gly-Ser-Ser-Cys-Ser-Xaa3-Thr-Ser-Xaa5-Asn-Cys-Cys-Arg-Ser-Cys-Asn-(SEQ ID NO:144) Xaa3-Xaa5-Thr-Lys-Arg-Cys-Xaa5-Gly-# Name: w-GVICSpecies: geographus Isolated: Yes Toxin Sequence:Cys-Lys-Ser-Xaa3-Gly-Ser-Ser-Cys-Ser-Xaa3-Thr-Ser-Xaa5-Asn-Cys-Cys-Arg-Ser-Cys-Asn-(SEQ ID NO:145) Xaa3-Xaa5-Thr-Lys-Arg-Cys-# Name: w-GVIIA Species:geographus Isolated: Yes Cloned: Yes DNA Sequence:CATCACAGCTGATGACTCCAGAGGTACGCAGAAGCATCGTGCCCTGAGGTCGTCCA (SEQ ID NO:146)CCAAACTCACCTTGTCGACTCGCTGCAAATCACCCGGAACTCCATGTTCAAGGGGTATGCGTGATTGCTGCACGTCTTGCTTGTTATACAGCAACAAATGTAGGCGCTACTAACCCAGCGCCTGATCTTCCCCCTTCTGTGCTCTATTCCTTTCTGCCTGAGTCCTCCTTACCTGAAAGTGGTCATGAACCACTCATCACCTACTTCTCTGGAGGCTTCAGAAGAGCTACATTGAAATAAAAGCCGCATTGCAATGAC Translation:ITADDSRGTQKHRALRSSTKLTLSTRCKSPGTPCSRGMRDCCTSCLLYSNKCRRY (SEQ ID NO:147)Toxin Sequence:Cys-Lys-Ser-Xaa3-Gly-Thr-Xaa3-Cys-Ser-Arg-Gly-Met-Arg-Asp-Cys-Cys-Thr-Ser-Cys-Leu-(SEQ ID NO:148) Leu-Xaa5-Ser-Asn-Lys-Cys-Arg-Arg-Xaa5-# Name: w-GVIIBSpecies: geographus Isolated: Yes Toxin Sequence:Cys-Lys-Ser-Xaa3-Gly-Thr-Xaa3-Cys-Ser-Arg-Gly-Met-Arg-Asp-Cys-Cys-Thr-Ser-Cys-Leu-(SEQ ID NO:149) Ser-Xaa5-Ser-Asn-Lys-Cys-Arg-Arg-Xaa5-# Name: La6.1Species: laterculatus Cloned: Yes DNA Sequence:ACCAAAACCATCATCAAAATGAAACTGACGTGTGTGGTGATCGTCGCCGTGCTGCT (SEQ ID NO:150)CCTGACGGCCTGTCAACTCATCACCGCTGATGACTCCAGAGGTACGCAGAAGCATCGTGCCCTGAGGTCGACCACCAATCTCTCCATGCTGACTCGGAAGTGCTGGCCTTCCGGAAGCTATTGTCGTGCGAATAGTAAATGCTGCAGTGGATGCGATCGGAACAGAAATAAATGTTACTAGCTGATTCGGCGTCTGAACTTCCTCCTTCTGTGCTCTATCCTTTTCTGCCCGAGTCCTCCATACCTGAGAGTGGTCATGAACCACTCAACTCCTACTCCTCTGGAGGCCTCAGAAGAGCTACATTGAAATAAAAGCCGCATTGC Translation:MKLTCVVIVAVLLLTACQLITADDSRGTQKHRALRSTTNLSMLTRKCWPSGSYCRANS (SEQ IDNO:151) KCCSGCDRNRNKCY Toxin Sequence:Lys-Cys-Xaa4-Xaa3-Ser-Gly-Ser-Xaa5-Cys-Arg-Ala-Asn-Ser-Lys-Cys-Cys-Ser-Gly-Cys-Asp-(SEQ ID NO:152) Arg-Asn-Arg-Asn-Lys-Cys-Xaa5-{circumflex over ( )} Name:La6.2 Species: laterculatus Cloned: Yes DNA Sequence:ACCAAAACCATCATCAAAATGAAACTGACGTGTGTGGTGATCGTCGCCGTGCTGCT (SEQ ID NO:153)CCTGACGGCCTGTCAACTCATCACAGCTGATGACTCCAGAGGTACGCAGAAGCATCGTGCCCTGAGGTCGACCACCAAACTCTCCATATCGACTCGCTGCCTTCCTCCCGGATCATATTGTAAGGCGACAACGGAAGTCTGCTGCTCTTCTTGCCTTCAATTCGCTCAGATATGTTCGGGTTGATCTTCCCTCTTCTGTGCTCTATCCTTTTCTGCCTGAGTCCTCCATACCTGAGAATGGTCATGAACCACTCAACATCTACTCCTCTGGAGGCCTCAGAAGAGCTATATTGAAATAAAAGCCGCATTGC Translation:MKLTCVVIVAVLLLTACQLITADDSRGTQKHRALRSTTKLSISTRCLPPGSYCKATTEVC (SEQ IDNO:154) CSSCLQFAQICSG Toxin Sequence:Cys-Leu-Xaa3-Xaa3-Gly-Ser-Xaa5-Cys-Lys-Ala-Thr-Thr-Xaa1-Val-Cys-Cys-Ser-Ser-Cys-Leu-(SEQ ID NO:155) Gln-Phe-Ala-Gln-Ile-Cys-Ser-# Name: La6.3 Species:laterculatus Cloned: Yes DNA Sequence:ACCAAAACCATCATCAAAATGAAACTGACGTGTGTGGTGATCGTCGCCGTGCTGCT (SEQ ID NO:156)CCTGACGGCCTGTCAACTCATCACAGCTGATGACTCCAGAGGTACGCAGAAGCATCGTGCCCTGAGGTCGACCACCAATCTCTCCATGTCGACTCGCTGCAAGTCTCCCGGATCATCATGTAGCGTGTCTATGCGTAACTGCTGCACTTCTTGCAATTCACGCACCAAGAAATGTACGCGACGTGGCTGAACTTCCCCCTTCTGTGCTCTATCCTTTTCTGCCCGAGTCCTCCATACCTGAGAGTGGTCATGAACCACTCAACATCTACTCCTCTGGAGGCCTCAGAAGAGCTATATTGAAATAAAAGCCGCATTGC Translation:MKLTCVVIVAVLLLTACQLITADDSRGTQKHRALRSTTNLSMSTRCKSPGSSCSVSMRN (SEQ IDNO:157) CCTSCNSRTKKCTRRG Toxin Sequence:Cys-Lys-Ser-Xaa3-Gly-Ser-Ser-Cys-Ser-Val-Ser-Met-Arg-Asn-Cys-Cys-Thr-Ser-Cys-Asn-Ser-(SEQ ID NO:158) Arg-Thr-Lys-Lys-Cys-Thr-Arg-Arg-# Name: La6.4 Species:laterculatus Cloned: Yes DNA Sequence:ACCAAAACCATCATCAAAATGAAACTGACGTGTGTGGTGATCGTCGCCGTGCTGCT (SEQ ID NO:159)CCTGACGGCCTGTCAACTCATCACAGCTGATGACTCCAGAGGTACGCAGAAGCATCGTGCCCTGAGGTCGACAACCAAACTCTCCATGCTGACTCGGACCTGCTGGCCTTCCGGAACAGCTTGTGGTATTGATAGTAACTGCTGCAGTGGATGCAATGTATCCAGAAGTAAATGTAACTAGCTGATTCGGCGTCTAAACTTCCTCCTTCTGCCTGAGTCCTCCATACCTGAGAGTGGTCATGAACCACATCATCACCTCATCTCTGGAGGCCTC Translation:MKLTCVVIVAVLLLTACQLITADDSRGTQKHRALRSTTKLSMLTRTCWPSGTACGIDSN (SEQ IDNO:160) CCSGCNVSRSKCN Toxin Sequence:Thr-Cys-Xaa4-Xaa3-Ser-Gly-Thr-Ala-Cys-Gly-Ile-Asp-Ser-Asn-Cys-Cys-Ser-Gly-Cys-Asn-(SEQ ID NO:161) Val-Ser-Arg-Ser-Lys-Cys-Asn-{circumflex over ( )} Name:La6.5 Species: laterculatus Cloned: Yes DNA Sequence:ACCAAAACCATCATCAAAATGAAACTGACGTGTGTGGTGATCGTCGCCGTGCTGCT (SEQ ID NO:162)CCTGACGGCCTGTCAACTCATCACAGCTGATGACTCCAGAGGTACGCAGAAGCATCGTGCCCTGAGGTCGACCACCAATCTCTCCATGCTGACTCGGAAGTGCTGGCCTTCCGGAAGCTATTGTCGTGCGAATAGTAAATGCTGCAGTGGATGCGATCGGAACAGAAGTAAATGTAACTAGCTGATTCGGCGTCTAAACTTCCTCCTTCTGCCTGAGTCCTCCATACCTGAGAGTGGTCATGAACCACTCATCACCTACTCCTCTGGAGGCCTCAAAGGAGCTACATTGAAATAAAAGCCGCATTGC Translation:MKLTCVVIVAVLLLTACQLITADDSRGTQKHRALRSTTNLSMLTRKCWPSGSYCRANS (SEQ IDNO:163) KCCSGCDRNRSKCN Toxin Sequence:Lys-Cys-Xaa4-Xaa3-Ser-Gly-Ser-Xaa5-Cys-Arg-Ala-Asn-Ser-Lys-Cys-Cys-Ser-Gly-Cys-Asp-(SEQ ID NO:164) Arg-Asn-Arg-Ser-Lys-Cys-Asn-{circumflex over ( )} Name:Lp6.1 Species: leopardus Cloned: Yes DNA Sequence:ATGAAACTGACGTGTGTGGTGATCGTAGCTGTGCTGTTCCTGACGGCCTGTCAACTC (SEQ IDNO:165) ACTACAGCTGACATCTCCAGAGGTACGCGGAAGCGTCGTGCTCTGAGGTCGACCACCAAACTCTCCAGGTCGCTCTTTGAGTGCGCGCCTTCCGGTGGACGTTGTGGTTTTTTAAAGTCCTGCTGCGAAGGATATTGCGATGGGGAAAGCACTTCATGTGTGAGTGGCCCATACAGCATCTGATCTTCCCGCCTTCAGTGCTCTATCCTTTTCTGCCTGAGTCCTCCATACCTCTGAGCGGTCATGAACCACTCAACACCTACTCCTCTGGAGGCTTCAGGGAACTATATTAAAATAAAGCCGCATTGCAACGAAANAAAAAAAAAAAAAAAAA Translation:MKLTCVVIVAVLFLTACQLTTADISRGTRKRRALRSTTKLSRSLFECAPSGGRCGFLKSC (SEQ IDNO:166) CEGYCDGESTSCVSGPYSI Toxin Sequence:Ser-Leu-Phe-Xaa1-Cys-Ala-Xaa3-Ser-Gly-Gly-Arg-Cys-Gly-Phe-Leu-Lys-Ser-Cys-Cys-Xaa1-(SEQ ID NO:167)Gly-Xaa5-Cys-Asp-Gly-Xaa1-Ser-Thr-Ser-Cys-Val-Ser-Gly-Xaa3-Xaa5-Ser-Ile-{circumflexover ( )} Name: Lp6.2 Species: leopardus Cloned: Yes DNA Sequence:ATGAAACTGACGTGTGTGGTGATCGTCGCTGTGCTGTTCCTGACGGCCTGTCAACTC (SEQ IDNO:168) ACTACAGCTGACATCTCCAGAGGTACGTGGAAGCATCGTGGTGTGGGGTCGACCACCGGACTCTCCCCGTGGCCCTTGGACTGCACGGCTCCCAGTCAACCTTGTGGTTATTTTCCTAGGTGCTGTGGACATTGCGATGTACGCAGGGTATGTACGAGTGGCTGATCCGGCGTCTGATCTTTCCGCCTTCTGTGCTGTATCCTTTTCTGCCTGAGTCCTCCATACCCGTGAGTGGTCATGAACCACTCAACACCTACTCCTCTGGAGGCTTCAGAGGAACTATATTAAAATAAAGCCGCATTGCAATG Translation:MKLTCVVIVAVLFLTACQLTTADISRGTWKHRGVGSTTGLSPWPLDCTAPSQPCGYFPR (SEQ IDNO:169) CCGHCDVRRVCTSG Toxin Sequence:Xaa4-Xaa3-Leu-Asp-Cys-Thr-Ala-Xaa3-Ser-Gln-Xaa3-Cys-Gly-Xaa5-Phe-Xaa3-Arg-Cys-Cys-(SEQ ID NO:170) Gly-His-Cys-Asp-Val-Arg-Arg-Val-Cys-Thr-Ser-# Name:Lp6.3 Species: leopardus Cloned: Yes DNA Sequence:ATGAAACTGACGTGTGTGGTGATCGTCGCTGTGCTGTTCCTGACGGCCTGTCAACTC (SEQ IDNO:171) ACTACAGCTGACATCTCCAGAGGTACGCGGAAGCATCGTGCTCTGAGGTCGACCACCAAACTCTCCAGGTCGCCCTCTAGGTGCATGTCTCCCGGTGGAATTTGTGGTGATTTTGGTGACTGCTGCGAAATTTGCAATGTGTACGGTATATGTGTGAGTGACTTACCCGGCATCTGATCTTTCCGCCTTCTGTGCTCTATCCTTTTCTGCCTGAGTCCTCCATACCCCTGAGTGGTCATGGACCACTCAACACCTACTCCTCTGGAGGCTTCAGAGGAACTACATTAAAATAAAGCCGCATTGCAAAAAAAAAAAAAAAAAAAAA Translation:MKLTCVVIVAVLFLTACQLTTADISRGTRKHRALRSTTKLSRSPSRCMSPGGICGDFGDC (SEQ IDNO:172) CEICNVYGICVSDLPGI Toxin Sequence:Cys-Met-Ser-Xaa3-Gly-Gly-Ile-Cys-Gly-Asp-Phe-Gly-Asp-Cys-Cys-Xaa1-Ile-Cys-Asn-Val-(SEQ ID NO:173)Xaa5-Gly-Ile-Cys-Val-Ser-Asp-Leu-Xaa3-Gly-Ile-{circumflex over ( )}Name: Lp6.4 Species: leopardus Cloned: Yes DNA Sequence:ATGAAACTGACGTGTGTGGTGATCGTCGCTGTGCTGTTCCTGACGGCCTGTCAACTC (SEQ IDNO:174) ACTACAGCTGATGATTCCAGAGGTACACGGAAGCATCGTGCTCTGAGGTCAACCACCAAACTCTCCAGGTGGCCCAGGTACTGCGCGCCTCCCGGTGGAGCTTGTGGGTTTTTTGATCACTGCTGCGGATATTGCGAAACGTTTTACAATACGTGTAGATGAGTTGGCTGATCCGGCGCTTGATCTTTCCGCCTTCTGTTGCTCTATCTTTTTCTGCCTGAGTCCTCCCATACCCCGTTGAGTGGTCCATGAACCACTCCAACACCTACTCCCTCCTTGGAAGCTTCCAAAGGAAACGACATTTAAAATAAATTCCCCATTGCAATTGGAAAAAAAAAAAAA AAAAATranslation: MKLTCVVIVAVLFLTACQLTTADDSRGTRKHRALRSTTKLSRWPRYCAPPGGACGFFD(SEQ ID NO:175) HCCGYCETFYNTCR Toxin Sequence:Xaa5-Cys-Ala-Xaa3-Xaa3-Gly-Gly-Ala-Cys-Gly-Phe-Phe-Asp-His-Cys-Cys-Gly-Xaa5-Cys-(SEQ ID NO:176) Xaa1-Thr-Phe-Xaa5-Asn-Thr-Cys-Arg-{circumflex over ( )}Name: L6.1 Species: lynceus Cloned: Yes DNA Sequence:ATGAAACTGACGTGTGTGGTGATCGTCGCCGTGCTGCTCCTGACGGCCTGTCAACTC (SEQ IDNO:177) ATCACAGCTGATGACTCCAGACGTACACAGAAGCATCGTGCCCTGAGGTCGACCACCAATCTCTCCATGTCGACTCGCTGCAAGTCTCCCGGATCACCATGTAGTGTGACATCGTATAACTGCTGCACTTTTTGCTCTTCATACACTAAGAAATGTCGGGCCTCTTTATGAACCACTCATCACCTACTCCTCTGGAGGCCTCAGAAGAGCTACACTGAAATAAAAGC CGCATTGGTranslation: MKLTCVVIVAVLLLTACQLITADDSRRTQKHRALRSTTNLSMSTRCKSPGSPCSVTSYN(SEQ ID NO:178) CCTFCSSYTKKCRASL Toxin Sequence:Cys-Lys-Ser-Xaa3-Gly-Ser-Xaa3-Cys-Ser-Val-Thr-Ser-Xaa5-Asn-Cys-Cys-Thr-Phe-Cys-Ser-(SEQ ID NO:179) Ser-Xaa5-Thr-Lys-Lys-Cys-Arg-Ala-Ser-Leu-{circumflexover ( )} Name: L6.2 Species: lynceus Cloned: Yes DNA Sequence:ATGAAACTGACGTGTGTGGTGATCGTCGCCGTGCTGCTCCTGACGGCCTGTCAACTC (SEQ IDNO:180) ATCACAGCTGATGACTCCAGAGGTACGCAGAAGCATCGTGCCCTGAGGTCGACCACCAAACTATCCATGTATACTCGCTGCGCAGGTCCAGGAGCAATTTGTCCTAATAGGGTATGCTGCGGTTATTGCAGTAAAAGAACACATCTATGTCATTCGCGAACTGGCTGATCTTCCCCCTTCTGTGCTCTATCCTTTTTCTGCCTGAGTCCTCCATACCTGAGAATGGTCATGAACCACTCATCACCTACTCCTCTTGGAGACCTCAGAGGAGCTACACTGAAATA AAAGCCGCATTGGCTranslation: MKLTCVVIVAVLLLTACQLITADDSRGTQKHRALRSTTKLSMYTRCAGPGAICPNRVCC(SEQ ID NO:181) GYCSKRTHLCHSRTG Toxin Sequence:Cys-Ala-Gly-Xaa3-Gly-Ala-Ile-Cys-Xaa3-Asn-Arg-Val-Cys-Cys-Gly-Xaa5-Cys-Ser-Lys-Arg-(SEQ ID NO:182) Thr-His-Leu-Cys-His-Ser-Arg-Thr-# Name: L6.3 Species:lynceus Cloned: Yes DNA Sequence:ATGAAACTGACGTGTGTGGTGATCGTCGCCGTGCTGCTGCTAGCGGCCTGTCAACTA (SEQ IDNO:183) CTACACGCTGATGACTCCAGAGGTACGCAGAAGACTGCTGCCCGAGGTCGACCACCAAAACTCTCCATGCTGACTCGGGCCTGCTGGTCTTCCGGAACACCTTGTGGTACTGATAGTTTATGCTGCGGTGGATGCAATGTATCCAAAAGTAAATGTAACTAGCTGATTCGGCGTCTGAACTTCCCCCTTCTGTGCTCTATCCTTTTCTGCCCGAGTCCTCCATACCTGAGAATGGTCATGAACCACTCATCACCTACTCCTCTGGAGACCTCAGAAGAGCTACACTGAAATAAAAGCGCATTGC Translation:MKLTCVVIVAVLLLAACQLLHADDSRGTQKTAAGRPPLSMLTRACCWSSGTPCGTDS (SEQ IDNO:184) LCCGGCNVSKSKCN Toxin Sequence:Ala-Cys-Xaa4-Ser-Ser-Gly-Thr-Xaa3-Cys-Gly-Thr-Asp-Ser-Leu-Cys-Cys-Gly-Gly-Cys-Asn-(SEQ ID NO:185) Val-Ser-Lys-Ser-Lys-Cys-Asn-{circumflex over ( )} Name:L6.4 Species: lynceus Cloned: Yes DNA Sequence:ATGAAACTGACGTGTGTGGTGATCGTCGCCGAGCTACTCCTAACGGCCTGTCAACTC (SEQ IDNO:186) ATCACAGCTGATGACTCCAGAGGTACGCAGAAGCATCGTGCCCTGAGGTCGACCACCAATCTCTCCATGCTGACTCGGAAGTGCTGGTCTCCCGGAACCTATTGTCGTGCGCATAGTAAATGCTGCCGTGGATGCGATCAGAACAGAAATAAATGTTACTAGCTGATTCGGCGTCTGAACTTCCTCCTTCTGTGCTCTATCCTTTTTCTGCCTGAGTCCTCCATACCTGAGAATGGTCATGAACCACTCATCACCTACTCCTCTGGAGGCCTCAGAGGAGCCTACACTGAAATAAAAGCCGCATTGG Translation:MKLTCVVIVAELLLTACQLITADDSRGTQKHRALRSTTNLSMLTRKCWSPGTYCRAHS (SEQ IDNO:187) KCCRGCDQNRNKCY Toxin Sequence:Lys-Cys-Xaa4-Ser-Xaa3-Gly-Thr-Xaa5-Cys-Arg-Ala-His-Ser-Lys-Cys-Cys-Arg-Gly-Cys-Asp-(SEQ ID NO:188) Gln-Asn-Arg-Asn-Lys-Cys-Xaa5-{circumflex over ( )} Name:M6.1 Species: magus Cloned: Yes DNA Sequence:ACCAAAACCATCATCAAAATGAAACTGACGTGTGTGGTGATCGTCGCCGTGCTGCT (SEQ ID NO:189)CCTGACGGCCTGTCAACTCATCACAGCTGATGACTCCAGAGGTACGCAGAAGCATCGTGCCCTGAGGTCGGACACCAAACTCTCCATGTCGACTCGCTGCAAGGGTACAGGAAAACCATGCAGTAGGATTGCGTATAACTGCTGCACCGGTTCTTGCAGATCAGGTAAATGTGGCTGATCCAGTGCCTGATCTTCCCCCTTCTGTGCTCTATCCTTTTTCTGCCTGAGTCCTCCTTACCTGAGAGTGGTCATGAACCACTCA Translation:MKLTCVVIVAVLLLTACQLITADDSRGTQKHRALRSDTKLSMSTRCKGTGKPCSRIAYN (SEQ IDNO:190) CCTGSCRSGKCG Toxin Sequence:Cys-Lys-Gly-Thr-Gly-Lys-Xaa3-Cys-Ser-Arg-Ile-Ala-Xaa5-Asn-Cys-Cys-Thr-Gly-Ser-Cys-(SEQ ID NO:191) Arg-Ser-Gly-Lys-Cys-# Name: M6.2 Species: magus Cloned:Yes DNA Sequence;ACCAAAACCATCATCAAAATGAAACTGACGTGTGTGGTGATCGTCGCCGTGCTGCT (SEQ ID NO:192)CCTGACGGCCTGTCAACTCATCACAGCTGATGACTCCAGAGGTACGCAGAAGCATCGTGCCCTGAAGTCGGACACCAAACTCTCCATGTTAACTTTGCGCTGCGCATCTTACGGAAAACCTTGTGGTATTTACAACGACTGCTGCAATACATGCGATCCAGCCAGAAAGACATGTACGTAGCTGATCCGGCGTCTGATCTTCC Translation:MKLTCVVIVAVLLLTACQLITADDSRGTQKHRALKSDTRLSMLTLRCASYGKPCGIYN (SEQ IDNO:193) DCCNTCDPARKTCT Toxin Sequence:Cys-Ala-Ser-Xaa5-Gly-Lys-Xaa3-Cys-Gly-Ile-Xaa5-Asn-Asp-Cys-Cys-Asn-Thr-Cys-Asp-(SEQ ID NO:194) Xaa3-Ala-Arg-Lys-Thr-Cys-Thr-{circumflex over ( )} Name:w-MVIIB Species: magus Isolated: Yes Cloned: Yes DNA Sequence:GAATTTTCAGCATCACCAAAACCATCATCAAAATGAAACTGACGTGTGTGGTGATC (SEQ ID NO:195)GTCGCCGTGCTGCTCCTGACGGCCTGTCAACTCATCACAGCTGATGACTCCAGAGGTACGCAGAAGCATCGTGCCCTGAGGTCGGACACCAAACTCTCCATGTCAACTCGCTGCAAGGGTAAAGGAGCATCATGTCATAGGACTTCGTATGACTGCTGCACCGGTTCTTGCAACAGAGGTAAATTTGGCTGATCCGCC Translation:MKLTCVVIVAVLLLTACQLITADDSRGTQKHRALRSDTKLSMSTRCKGKGASCHRTSY (SEQ IDNO:196) DCCTGSCNRGKFG Toxin Sequence:Cys-Lys-Gly-Lys-Gly-Ala-Ser-Cys-His-Arg-Thr-Ser-Xaa5-Asp-Cys-Cys-Thr-Gly-Ser-Cys-Asn-(SEQ ID NO:197) Arg-Gly-Lys-Cys-# Name: Mi6.1 Species: miles Cloned: YesDNA Sequence: GGATCCATGAAACTGACGTGCGTGGTGATCATCGCCATGCTGTTCCTGACAGCCTAT(SEQ ID NO:198) CAACTCGCTACAGCTGCGAGCTACGCCAAAGGTAAACAGAAGCATCGTGCTCTGAGGCCAGCTGACAAACACCTCAGGTTGACCAAGCGTTGCAATGATCGCGGTGGAGGTTGCAGTCAACATCCTCACTGCTGCGGTGGAACTTGCAATAAGCTTATTGGCGTATGTCTGTAAAGCTGGTCTGCCGTCTGATATTCCCTTTCTGTGCTTCATCCTCTTTTGCCTGAGTCATCCATACCTGTGAATGGTTAAGAGCCACTCAATACCTATTCCTCTGGGGGCTTCAGAGGAACTACTTTAC Translation:MKLTCVVIIAMLFLTAYQLATAASYAKGKQKHRALRPADKHLRLTKRCNDRGGGCSQ (SEQ IDNO:199) HPHCCGGTCNKLIGVCL Toxin Sequence:Cys-Asn-Asp-Arg-Gly-Gly-Cys-Ser-Gln-His-Xaa3-His-Cys-Cys-Gly-Gly-Thr-Cys-Asn-(SEQ ID NO:200) Lys-Leu-Ile-Gly-Val-Cys-Leu-{circumflex over ( )} Name:Mn6.1 Species: monachus Cloned: Yes DNA Sequence:ACCAAAACCATCATCAAAATGAAACTGACGAGTGTGGTGATCGTCGCCGTGCTGCT (SEQ ID NO:201)CCTGACGGCCTGTCAACTCATCACAGCTGATGACTCCAGAGGTACGCAGAAGCATCGTGCCCTGAGGTCGGACACCAAACTCTCCATATCGACTCGCTGCAAGTCTACAGGAAAATCATGCAGTAGGATTGCGTATAACTGCTGCACCGGTTCTTGCAGATCAGGTAAATGTGGCTGATCCAGCGCCTGATCTTCCCCCTTCTGTGCTCTATCCTTTTCTGCCTGA GTCCTCCTTATranslation:MKLTSVVIVAVLLLTACQLITADDSRGTQKHRALRSDTKLSISTRCKSTGKSCSRIAYNC (SEQ IDNO:202) CTGSCRSGKCG Toxin Sequence:Cys-Lys-Ser-Thr-Gly-Lys-Ser-Cys-Ser-Arg-Ile-Ala-Xaa5-Asn-Cys-Cys-Thr-Gly-Ser-Cys-Arg-(SEQ ID NO:203) Ser-Gly-Lys-Cys-# Name: Mn6.2 Species: monachus Cloned:Yes DNA Sequence:ACCAAAACCATCATCAAAATGAAACTGACGAGTGTGGTGATCGTCGCCGTGCTGCT (SEQ ID NO:204)CCTGACGGCCTGTCAACTCATCACAGCTGATGACTCCAGAGGTACGCAGAAGCATCGTGCCCTGAGGTCGGACACCAACCTCTCCATGTCGACTCGCTGCAAGGGTAAAGGATCTTCATGTAGTAGGACCATGTATAACTGCTGCACCGGTTCTTGCAACAGAGGTAAATGTGGCTGATCCAGCGCCTGATCTTCCCCCTTC Translation:MKLTSVVIVAVLLLTACQLITADDSRGTQKHRALRSDTNLSMSTRCKGKGSSCSRTMY (SEQ IDNO:205) NCCTGSCNRGKCG Toxin Sequence:Cys-Lys-Gly-Lys-Gly-Ser-Ser-Cys-Ser-Arg-Thr-Met-Xaa5-Asn-Cys-Cys-Thr-Gly-Ser-Cys-(SEQ ID NO:206) Asn-Arg-Gly-Lys-Cys-# Name: O6.1 Species: obscurusCloned: Yes DNA Sequence:ctctctctctctctgctggacAGGTCGCCTCCCTGCATGAAAGGCGGATCGTCATGCCGCGGTAC (SEQID NO:207) TACGGGAGTCTGTTGCGGTTTTTGCAGTGATTTCGGCTATAAATGTAGGGACTATCCCCAAAACTGATCTTCCCCCTTCTGTGCTCTATCCTTTTCTGTCCGAGTCCTCCTGACCTGAGAGTGGTCATGAACCACTCATCACCTACCCCTCTGGGGCTTCACAGGATCTACATTGAAATAAAAGCCGCATTGC Translation:LLDRSPPCMKGGSSCRGTTGVCCGFCSDFGYKCRDYPQN (SEQ ID NO:208) Toxin Sequence:Ser-Xaa3-Xaa3-Cys-Met-Lys-Gly-Gly-Ser-Ser-Cys-Arg-Gly-Thr-Thr-Gly-Val-Cys-Cys-Gly-(SEQ ID NO:209)Phe-Cys-Ser-Asp-Phe-Gly-Xaa5-Lys-Cys-Arg-Asp-Xaa5-Xaa3-Gln-Asn-{circumflexover ( )} Name: O6.2 Species: obscurus Cloned: Yes DNA Sequence:ctctctctctctctgctggacAGGTCGACTCGCTGCTTGCCTGACGGAACGTCTTGCCTTTTTAGT (SEQID NO:210) AGGATCAGATGCTGCGGTACTTGCAGTTCAATCTTAAAGTCATGTGTGAGCTGATCCAGCGGTTGATCTTCCTCCCTCTGTGCTCCATCCTTTTCTGCCTGAGTTCTCCTTACCTGAGAGTGGTCATGAACCACTCATCACCTACTCTTCTGGAGGCTTCAGAGGAGCTACATTGAAATAAAAGCCGCATTGC Translation: RSTRCLPDGTSCLFSRIRCCGTCSSILKSCVS(SEQ ID NO:211) Toxin Sequence:Cys-Leu-Xaa3-Asp-Gly-Thr-Ser-Cys-Leu-Phe-Ser-Arg-Ile-Arg-Cys-Cys-Gly-Thr-Cys-Ser-Ser-(SEQ ID NO:212) Ile-Leu-Lys-Ser-Cys-Val-Ser-{circumflex over ( )} Name:Pu6.2 Species: pulicarius Cloned: Yes DNA Sequence:ATGAAACTGACGTGTGTGGTGATCATCGCCGTGCTGTTCCTGACGGCCTGTCAACTC (SEQ IDNO:213) ATTACAGCTGAGACTTACTCCAGAGGTAAGCAGAAGCACCGTGCTTTGAGGTCAACTGACAAAAACTCCAAGTTGACTAGGCAGTGCTCGCCTAACGGTGGATCTTGTTCTCGTCATTTTCACTGCTGCAGCCTCTATTGCAATAAAAATACTGGCGTATGTATTGCAACCTAATACCCGTGTGTGGTCATGAACCACTCAATACCCTCTCCTCTGGAGGCTTCAGAGGAACTGCATTGAAATAAAACTGCATTGCNTTGACCAAAAAAAAAA Translation:MKLTCVVIIAVLFLTACQLITAETYSRGKQKHRALRSTDKNSKLTRQCSPNGGSCSRHF (SEQ IDNO:214) HCCSLYCNKNTGVCIAT Toxin Sequence:Xaa2-Cys-Ser-Xaa3-Asn-Gly-Gly-Ser-Cys-Ser-Arg-His-Phe-His-Cys-Cys-Ser-Leu-Xaa5-Cys-(SEQ ID NO:215) Asn-Lys-Asn-Thr-Gly-Val-Cys-Ile-Ala-Thr-{circumflex over( )} Name: P6.1 Species: purpurascens Cloned: Yes DNA Sequence:ATGAAACTGACGTGTGTGGTGATCGTCGCCGTGCTGTTCCTGACGGCCTGTCAACTC (SEQ IDNO:216) ATCACAGCTGATGACTCCAGACGTACGCAGAAGCATCGTGCCCTGAGGTCGACCACCAAAGGCGCCACGTCGAATCGCCCCTGCAAGACACCCGGACGAAAATGTTTTCCGCATCAGAAGGACTGCTGCGGTCGAGCGTGCATCATCACAATATGTCCCTGATCTTCCCCCTTCTGTGCTGTATCCTTTTCTGCCTGAGTCTCCTTACCTGAGAGTGGTCATGAA Translation:MKLTCVVIVAVLFLTACQLITADDSRRTQKHRALRSTTKGATSNRPCKTPGRKCFPHQK (SEQ IDNO:217) DCCGRACIITICP Toxin Sequence:Xaa3-Cys-Lys-Thr-Xaa3-Gly-Arg-Lys-Cys-Phe-Xaa3-His-Gln-Lys-Asp-Cys-Cys-Gly-Arg-Ala-(SEQ ID NO:218) Cys-Ile-Ile-Thr-Ile-Cys-Xaa3-{circumflex over ( )} Name:P6.2 Species: purpurascens Isolated: Yes Cloned: Yes DNA Sequence:ACCAAAACCATCATCAAAATGAAACTGACGTGTGTGGTGATCGTCGCCGTGCTGCT (SEQ ID NO:219)CCTGACGGCCTGTCAACTCATCACAGCTGATGACTCCAGAGGTACGCAGAAGCATCGTGCCCTGAGGTCGACCACCAAACTCTTCACGTCGAAAAGCTGCAAGCTTCCCGGAGCATATTGTAATGCAGAAGATTATGACTGCTGCCTTAGATGCAAAGTTGGAGGTACATGTGGCTGATCCAGTGCCTGATCTTCCCCCTTCTGTGCTCTATCCTTTTCTGCCTGAGTCCTCCTTACCTAAGAGTGGTCATGAACCACTCATCACCTTCTCCTCTGGAGGCTT C Translation:MKLTCVVIVAVLLLTACQLITADDSRGTQKHRALRSTTKLFTSKSCKLPGAYCNAEDYD (SEQ IDNO:220) CCLRCKVGGTCG Toxin Sequence:Ser-Cys-Lys-Leu-Xaa3-Gly-Ala-Xaa5-Cys-Asn-Ala-Xaa1-Asp-Xaa5-Asp-Cys-Cys-Leu-Arg-(SEQ ID NO:221) Cys-Lys-Val-Gly-Gly-Thr-Cys-# Name: P6.3 Species:purpurascens Cloned: Yes DNA Sequence:ATGAAACTGACGTGTGTGGTGATCGTCGCCGTGCTGTTCCTGACGGCCTGTCAACTC (SEQ IDNO:222) ATCACAGCTGATGACTCCAGACGTACGCAGAAGCATCGTGCCCTGAGGTCGACCACCAAACGCGCCACGTCGAATCGCCCCTGCAAGAAAACCGGACGAAAATGTTTTCCGCATCAGAAGGACTGCTGCGGTCGAGCGTGCATCATCACAATATGTCCCTGATCTTCCCCCTTCTGTGCTGTATCCTTTTCTGCCTGAGTCCTCCTTACCTGAGAGTGGTCATGAACCACTCATCACCTTCTCCTCTGGAGGCTTCAGAG Translation:MKLTCVVIVAVLFLTACQLITADDSRRTQKHRALRSTTKRATSNRPCKKTGRKCFPHQK (SEQ IDNO:223) DCCGRACIITICP Toxin Sequence:Xaa3-Cys-Lys-Lys-Thr-Gly-Arg-Lys-Cys-Phe-Xaa3-His-Gln-Lys-Asp-Cys-Cys-Gly-Arg-Ala-(SEQ ID NO:224) Cys-Ile-Ile-Thr-Ile-Cys-Xaa3-{circumflex over ( )} Name:R6.1 Species: radiatus Cloned: Yes DNA Sequence:GCTGATGCCTGATCTTCATCGTTCTTCCCTGTCTCCTTTGGCATCACCAAAACCATCA (SEQ IDNO:225) TCAAAATGAAACTGACGTGTGTGGTGATCGTCGCCGTGCTGGTCCTGACGGCCTGTCAACTCATCACAGCTGATGACTCCAGAGGTATGCAGAAACATCATGCCCTGGGGTCGATCAGCAGTCTCTTTAAGTCGACCCGTCATGGCTGCAAACCCCTCAAACGTCGTTGTTTCAATGATAAAGAATGCTGCAGCAAATTTTGCAATTCAGTCCGAAAGCAGTGTGGATAAATGGCTAAAAAACTGAATAAAAGCCGCATTGCAAAAAAAA Translation:MKLTCVVIVAVLVLTACQLITADDSRGMQKHHALGSISSLFKSTRHGCKPLKRRCFNDK (SEQ IDNO:226) ECCSKFCNSVRKQCG Toxin Sequence:His-Gly-Cys-Lys-Xaa3-Leu-Lys-Arg-Arg-Cys-Phe-Asn-Asp-Lys-Xaa1-Cys-Cys-Ser-Lys-Phe-(SEQ ID NO:227) Cys-Asn-Ser-Val-Arg-Lys-Gln-Cys-# Name: R6.2 Species:radiatus Cloned: Yes DNA Sequence:GAAATGAAACTGACGTGTGTGGTGATCGTCGCCGTGCTGGTCCTGACGGCCTGTCA (SEQ ID NO:228)ACTCATCACAGCTGATGACTCCAGAGGTATGCAGAAACATCATGCCCTGGGGTCGATCAGCAGTCTCTTTAAGTCGACCCGTCGTGGCTGCAAACCCCTCAAACGTCGTTGTTTCAATGATAAAGAATGCTGCAGCAAATTTTGCAATTCAGTCCGAAACCAGTGTGGATAAATGGCTAAAAACTGAATAAAAG Translation:MKLTCVVIVAVLVLTACQLITADDSRGMQKHHALGSISSLFKSTRRGCKPLKRRCFNDK (SEQ IDNO:229) ECCSKFCNSVRNQCG Toxin Sequence:Arg-Gly-Cys-Lys-Xaa3-Leu-Lys-Arg-Arg-Cys-Phe-Asn-Asp-Lys-Xaa1-Cys-Cys-Ser-Lys-Phe-(SEQ ID NO:230) Cys-Asn-Ser-Val-Arg-Asn-GIn-Cys-# Name: w-RVIA Species:radiatus Cloned: Yes DNA Sequence:GGAATTCCGCTTGCACGGCGAACCTGACTTCATCTTTCTTCCCTGCCTCCTTTGGCAT (SEQ IDNO:231) CACCAAAACCATCATCAAAATGAAACTGACGTGTGTGGTGATCGTCGCCGTGCTGGTCCTGACGGCCTGTCAACTCATCACAGCTGATGACTCCAGAGGTATGCAGAAGCATCATGCCCTGAGGTCGATCACCAAACTCTCCCTGTCGACTCGCTGCAAACCTCCCGGATCACCATGTAGAGTTTCTTCGTATAACTGCTGCTCTTCTTGCAAATCATACAACAAGAAATGTGGCTGAACTTCCCCTTCTGTGCTCTATCCTTTTCCTGCCCGAGTCCTCCATACCTGAGAGTAGTCATGAACCACTGATTACCTACTCCTCTGGAGGGCCTCAGAGGAGCTACTTTGAAATAAAAGCCCGCATTGCAAAAAAAAAA Translation:MRLTCVVIVAVLVLTACQLITADDSRGMQKHHALRSITKLSLSTRCKPPGSPCRVSSYN (SEQ IDNO:232) CCSSCKSYNKKCG Toxin Sequence:Cys-Lys-Xaa3-Xaa3-Gly-Ser-Xaa3-Cys-Arg-Val-Ser-Ser-Xaa5-Asn-Cys-Cys-Ser-Ser-Cys-Lys-(SEQ ID NO:233) Ser-Xaa5-Asn-Lys-Lys-Cys-Gly-# Name: Ra6.1 Species:rattus Cloned: Yes DNA Sequence:GGATCCATGAAACTGACGTGCATGGTGATCATCGCCGTGCTGTTCCTGACAGCCTGT (SEQ IDNO:234) CAATTCGATACAGCTGCGAGCTACGACAAAGGTAAGCAGAAACCTCCTACTCTGAGGCCAGCTGACAAACACATCAGGTTGACCAAGCGTTGCAATGCTCGCAATGATGGTTGCAGTCAACATTCTCAATGCTGCAGTGGATCTTGCAATAAGACTGCAGGCGTATGTCTGTAAAGCTGGTCTGCCGTCTGATATTCCCTTTCTGTGCTTTATCCTCTTTTGCCTGAGTCATCCATACCTGTGAATGGTTAAGAGCCACTCAATACCTACTCCTCTGGGGGCTTCAGAGGAACTACATTAAATAAAGCCACATTGCAAAAAAAAAAAAAAAAAAA Translation:MKLTCMVIIAVLFLTACQFDTAASYDKGKQKPPTLRPADKHIRLTKRCNARINDGCSQH (SEQ IDNO:235) SQCCSGSCNKTAGVCL Toxin Sequence:Cys-Asn-Ala-Arg-Asn-Asp-Gly-Cys-Ser-Gln-His-Ser-Gln-Cys-Cys-Ser-Gly-Ser-Cys-Asn-Lys-(SEQ ID NO:236) Thr-Ala-Gly-Val-Cys-Leu-{circumflex over ( )} Name:Ra6.2 Species: rattus Cloned: Yes DNA Sequence:GGATCCATGAAACTGACGTGCGTGGTGATCATCGCCGTGCTGTTCCTGACAGCCTGT (SEQ IDNO:237) CAACTCGATGCAGCTGCGAGCTACGACAAAGGTAAGCAGAAACCTCCTACTCTGAGGCCAGCTGACAAACACTTCAGGTTGATCAAGCGTTGCAATGCTCGCAATAGTGGTTGCAGTCAACATCCTCAATGCTGCAGTGGATCTTGCAATAAGACTGCAGGCGTATGTCTGTAAAGCTGGTCTGCCGTCTGATATTCCCTTTCTGTGCTTTATCCTCTTTTGCCTGAGTCATCCATACCTGTGAATGGTTAAGAGCCACTCAATACCTACTCCTCTGGGGGCTTCAGAGGAACTACATTAAATAAAGCCACATTGCAACGAAAAAAAAAAAAAAAAAA Translation:MKLTCVVIIAVLFLTACQLDAAASYDKGKQKPPTLRPADKHFRLIKRCNARNSGCSQHP (SEQ IDNO:238) QCCSGSCNTAGVCL Toxin Sequence:Cys-Asn-Ala-Arg-Asn-Ser-Gly-Cys-Ser-Gln-His-Xaa3-Gln-Cys-Cys-Ser-Gly-Ser-Cys-Asn-(SEQ ID NO:239) Lys-Thr-Ala-Gly-Val-Cys-Leu-{circumflex over ( )} Name:Ra6.3 Species: rattus Cloned: Yes DNA Sequence:GGATCCATGAAACTGACGTGTGTGGTGATCATCGCCGTGCTGTTCCTGACAGCCTGT (SEQ IDNO:240) CAATTCGATACAGCTGCGAGCTACGACAAAGGTAAGCAGAAACCTCCTACTCTGAGGCCAGCTGACAAACACTTCAGGTTGATCAAGCGTTGCAATGCTCGCAATAGTGGTTGCAGTCAACATCCTCAATGCTGCAGTGGATCTTGCAATAAGACTTTGGGCGTATGTCTGTAAAGCTGGTCTGCCGTCTGATATTCCCTTTCTGTGCTTTATCCTCTTTTGCCTGAGTCATCCATACCTGTGAATGGTTAAGAGCCACTCAATACCTACTCCTCTGGGGGCTTCAGAGGAACTACATTAAATAAAGCCACATTGAAAAAAAAAAAAAAAAAA Translation:MKLTCVVIIAVLFLTACQFDTAASYDKGKQKPPTLRPADKHFRLIKRCNARNSGCSQHP (SEQ IDNO:241) QCCSGSCNKTLGVCL Toxin Sequence:Cys-Asn-Ala-Arg-Asn-Ser-Gly-Cys-Ser-Gln-His-Xaa3-Gln-Cys-Cys-Ser-Gly-Ser-Cys-Asn-(SEQ ID NO:242) Lys-Thr-Leu-Gly-Val-Cys-Leu-{circumflex over ( )} Name:Sm6.1 Species: stercusmuscarum Cloned: Yes DNA Sequence:ACCAAAACCATCATCAAAATGAAACTGACGTGTGTGGTGATCGTCGCCGTGCTGCT (SEQ ID NO:243)CCTGACGGCCTGTCAACTCATCACAGCTGATGACTCCAGAGGTACGCAGAAGCATCGTGCCCTGAGGTCGAAGACCAAACTCTCCATGTCGACTCGCTGCAAGAGTAAAGGAGCAAAATGTTCAAGGCTTATGTATGACTGCTGCAGCGGTTCTTGCAGCGGCTACACAGGTAGATGTGGCTGATCCAGCGCCTGATCTTCCCCCTTCTGTGCTCTATCCTTTTCTGCCTGGGTCCTCCTTACCTGAGAGTGGTCATGAACCACTCATCACCTACTCCTCTGGAGGCCTCAGAGGAGTTACAATGAAATAAAAGCCGCATTGC Translation:MKLTCVVIVAVLLLTACQLITADDSRGTQKHRALRSKTKLSMSTRCKSKGAKCSRLMY (SEQ IDNO:244) DCCSGSCSGYTGRCG Toxin Sequence:Cys-Lys-Ser-Lys-Gly-Ala-Lys-Cys-Ser-Arg-Leu-Met-Xaa5-Asp-Cys-Cys-Ser-Gly-Ser-Cys-Ser-(SEQ ID NO:245) Gly-Xaa5-Thr-Gly-Arg-Cys-# Name: Sm6.2 Species:stercusmuscarum Isolated: Yes Toxin Sequence:Thr-Thr-Ser-Cys-Met-Gln-Ala-Gly-Ser-Xaa5-Cys-Gly-Ser-Thr-Thr-Arg-Ile-Cys-Cys-Gly-Xaa5-(SEQ ID NO:246)Cys-Ala-Xaa5-Phe-Gly-Lys-Lys-Cys-Ile-Asp-Xaa5-Xaa3-Ser-Asn-{circumflexover ( )} Name: Sm6.3 Species: stercusmuscarum Cloned: Yes DNA Sequence:ACCAAAACCATCATCAAAATGAAACTGACGTGTGTGGTGATCGTCGCCGTGCTGCT (SEQ ID NO:247)CCTGACGACCTGTCAACTCATCACAGCTGATGACTCCAGAGGTACGCAGGAGCATCGTGCCCTGAGGTCGAAGACCAAACTCTCCATGTTAACTTTGCGCTGCGCATCTTACGGAAAACCTTGTGGTATTGACAACGACTGCTGCAATGCATGCGATCCAGCCAGAAATATATGTACGTAGCTGATCCGGCGTCTGATCTTCCCCCTTCTGTGCTCTATCCTTTTCTGCCTGAGTCCTCCTTACCTGAGAGTGGTCATGAACCACTCATCATCTACTCTCCTGGAGGCCTCAGAGGAGCTACAATGAAATAAAAGCCGCATTGC Translation:MKLTCVVIVAVLLLTTCQLITADDSRGTQEHRALRSKTKLSMLTLRCASYGKPCGIDND (SEQ IDNO:248) CCNACDPARNICT Toxin Sequence:Cys-Ala-Ser-Xaa5-Gly-Lys-Xaa3-Cys-Gly-Ile-Asp-Asn-Asp-Cys-Cys-Asn-Ala-Cys-Asp-Xaa3-(SEQ ID NO:249) Ala-Arg-Asn-Ile-Cys-Thr-{circumflex over ( )} Name:Sm6.4 Species: stercusmuscarum Cloned: Yes DNA Sequence:GGATCCATGAAACTGACGTGTGTGGTGATTGTCGCCGTGCTGCTCCTGACGGCCTGT (SEQ IDNO:250) CAACTCATCACAGCTGATGACTCCAGAGGTACGCAGGAGCATCGTGCCCTGAGGTCGAAGACCAAACTCTCCATGTTAACTTTGCGCTGCGTATCTTACGGAAAACCTTGTGGTATTGACAACGACTGCTGCAATGCATGCGATCCAGCCAGAAATATATGTACGTAGCTGATCCGGCGTCTGATCTTCCCCCTTCTGTGCTCTATCCTTTTCTGCCTGGGTCCTCCTTACCTGAGAGTGGTCATGAACCACTCATCACCTACTCCTCTGGAGGCCTCAGAGGAGTTACAATGAAATAAAAGCCGCATTGCAAAAAAAAAAAAAAAAAAAA Translation:MKLTCVVIVAVLLLTACQLITADDSRGTQEHRALRSKTKLSMLTLRCVSYGKLPCGIDND (SEQ IDNO:251) CCNACDPARNICT Toxin Sequence:Cys-Val-Ser-Xaa5-Gly-Lys-Xaa3-Cys-Gly-Ile-Asp-Asn-Asp-Cys-Cys-Asn-Ala-Cys-Asp-Xaa3-(SEQ ID NO:252) Ala-Arg-Asn-Ile-Cys-Thr-{circumflex over ( )} Name: S6.1Species: striatus Cloned: Yes DNA Sequence:ACCAAAACCATCATCAAAATGAAACTGACGTGTGTGGTGATCGTCGCCGTGCTGCT (SEQ ID NO:253)CCTGACGGCCTGTCAACTCATCACAGCTGATGACTCCAGAGGTACGCAGAAGCATCGTTCCCTGAGGTCGACCACCAAAGTCTCCAAGGCGACTGACTGCATTGAAGCCGGAAATTATTGCGGACCTACTGTTATGAAAATCTGCTGCGGCTTTTGCAGTCCATACAGCAAAATATGTATGAACTATCCCAAAAATTGATCTTCCCCC Translation:MKLTCVVIVAVLLLTACQLITADDSRGTQKHRSLRSTTKVSKATDCIEAGNYCGPTVM (SEQ IDNO:254) KICCGFCSPYSKICMNYPKN Toxin Sequence:Ala-Thr-Asp-Cys-Ile-Xaa1-Ala-Gly-Asn-Xaa5-Cys-Gly-Xaa3-Thr-Val-Met-Lys-Ile-Cys-Cys-(SEQ ID NO:255)Gly-Phe-Cys-Ser-Xaa3-Xaa5-Ser-Lys-Ile-Cys-Met-Asn-Xaa5-Xaa3-Lys-Asn-{circumflexover ( )} Name: S6.2 Species: striatus Cloned: Yes DNA Sequence:GTCGACTCGCTGCAAGCTTAAAGGACAATCATGTCGTAGGACTATGTATGACTGCTG (SEQ IDNO:256) CAGCGGTTCTTGCGGCAGGAGAGGTAAATGTGGCTGATCCAGCGCCTGATCTCCCCCCTTCTGTGCTCTATCCTTTTCTGCCTGGGTCCTCCTTACCTGAGAGTGGTCATGAACCACTCATCACCTACTCCTCTGGAGGCCTCAGAGGAGCTACAATGAAATAAAAGCCG CATTGCTranslation: STRCKLKGQSCRRTMYDCCSGSCGRRGKCG (SEQ ID NO:257) ToxinSequence:Cys-Lys-Leu-Lys-Gly-Gln-Ser-Cys-Arg-Arg-Thr-Met-Xaa5-Asp-Cys-Cys-Ser-Gly-Ser-Cys-(SEQ ID NO:258) Gly-Arg-Arg-Gly-Lys-Cys-# Name: S6.3 Species: striatusCloned: Yes DNA Sequence:ACCAAAACCATCATCAAAATGAAACTGACGTGTGTGGTGATCGTCGCCGTGCTGCT (SEQ ID NO:259)CCTGACGGCCTGTCAACTCATCACAGCTGATGACTCCAGAGGTACGCAGAAGCATCGTGCCCTGAGGTCGGACACCAAACTCTCCATGTCGACTCGCTGCAAGGCTGCAGGAAAATCATGCAGTAGGATTGCGTATAACTGCTGCACCGGTTCTTGCAGATCAGGTAAATGCGGCTGATCCAGCGCCTGATCTTCCCCCTTCTGTGCTCTATCCTTTCTGCCTGAGTCCTCTTACCTGAGAGTGGTCATGAACC Translation:MKLTCVVIVAVLLLTACQLITADDSRGTQKHRALRSDTKLSMSTRCKAAGKSCSRIAYN (SEQ IDNO:260) CCTGSCRSGKCG Toxin Sequence:Cys-Lys-Ala-Ala-Gly-Lys-Ser-Cys-Ser-Arg-Ile-Ala-Xaa5-Asn-Cys-Cys-Thr-Gly-Ser-Cys-Arg-(SEQ ID NO:261) Ser-Gly-Lys-Cys-# Name: S6.6 Species: striatus Cloned:Yes DNA Sequence:ACCAAAACCATCATCAAAATGAAACTGACGTGTGTGGTGATCGTCGCCGTGCTGCT (SEQ ID NO:262)CCTGACGGCCTGTCAACTCATCACAGCTGATGACTCCAGAGGTACGCAGGAGCATCGTGCCCTGAGGTCGGACACCAAACTCTCCATGTTAACTTTGCGCTGCGAATCTTACGGAAAACCTTGTGGTATTTACAACGACTGCTGCAATGCATGCGATCCAGCCAAAAAGACATGTACGTAGCTGATCCGGCGTCTGATCT Translation:MKLTCVVIVAVLLLTACQLITADDSRGTQEHRALRSDTKLSMLTLRCESYGKPCGIYND (SEQ IDNO:263) CCNACDPAKKTCT Toxin Sequence:Cys-Xaa1-Ser-Xaa5-Gly-Lys-Xaa3-Cys-Gly-Ile-Xaa5-Asn-Asp-Cys-Cys-Asn-Ala-Cys-Asp-(SEQ ID NO:264) Xaa3-Ala-Lys-Lys-Thr-Cys-Thr-{circumflex over ( )} Name:w-SVIA Species: striatus Cloned: Yes DNA Sequence:ACTAGGTCCTCCGGCAGCCCCTGTGGTGTTACTAGTATATGCTGTGGTAGATGCTAT (SEQ IDNO:265) AGGGGTAAATGTACGTAGCTCATCGGGCGTCTGATCTTCCCCCTTCTGTGCTCCATCCTTTTCTGCCTGAGTCCTCCTTACCTGAGAGTGGTCGTGAACCACTCATCGCCTACTCCTCTGGAGGCTTCAGAGGGGCTACACTAAAATAAAAGCTATATTGCAATGAAAAA A Translation:CRSSGSPCGVTSICCGRCYRGKCT (SEQ ID NO:266) Toxin Sequence:Cys-Arg-Ser-Ser-Gly-Ser-Xaa3-Cys-Gly-Val-Thr-Ser-Ile-Cys-Cys-Gly-Arg-Cys-Xaa5-Arg-(SEQ ID NO:267) Gly-Lys-Cys-Thr-# Name: w-SVIB Species: striatusIsolated: Yes Toxin Sequence:Cys-Lys-Leu-Lys-Gly-Gln-Ser-Cys-Arg-Lys-Thr-Ser-Xaa5-Asp-Cys-Cys-Ser-Gly-Ser-Cys-Gly-(SEQ ID NO:268) Arg-Ser-Gly-Lys-Cys-# Name: Sx6.1 Species: striolatusCloned: Yes DNA Sequence:ACCAAAACCATCATCAAAATGAAACTGACGTGTGTGGTGATCGTCGTCTTGCTGCTC (SEQ IDNO:269) CTCACGACCTGTCGTCTCATCACAGCTGATGACTCCAGAGGTACGCAGAAGCATCGTTCCCTGAGGTCGACTACTAAAGTCTCCATGTCGACTCGCTGCAAGGGTAAAGGAGCATCATGTCTTAGGACTGCGTATGACTGCTGCACCGGTTCTTGCAACAGAGGTAGATGTGGCTGATCCAGCGTCTGATCTTCCCCCTTCTGTGCTCTATCCTTTTCTGCTTGAGT CCTCCTTATranslation: MKLTCVVIVVLLLLTTCRLITADDSRGTQKHRSLRSTTKVSMSTRCKGKGASCLRTAYD(SEQ ID NO:270) CCTGSCNRGRCG Toxin Sequence:Cys-Lys-Gly-Lys-Gly-Ala-Ser-Cys-Leu-Arg-Thr-Ala-Xaa5-Asp-Cys-Cys-Thr-Gly-Ser-Cys-(SEQ ID NO:271) Asn-Arg-Gly-Arg-Cys-# Name: Sx6.2 Species: striolatusCloned: Yes DNA Sequence:ACCAAAACCATCATCAAAATGAAACTGACGTGTGTGGTGATCGTCGCCGTTCTGCTG (SEQ IDNO:272) ACGGCGTGTCAACTCATCACAGCTGAGGACTCCAGAGGTACACAGAAGCATCGTACCCTGAGGTCGACCGTCAGACGCTCCAAGTCCGAGTTGACTACGAGATGCAGGCCTTCAGGATCCAACTGTGGTAATATTAGTATCTGCTGTGGTAGATGCGTTAACAGAAGATGTACGTAGCTCATCGGGCGTCTGATCTTTCCCC Translation:MKLTCVVIVAVLLTACQLITAEDSRGTQKHRTLRSTVRRSKSELTTRCRPSGSNCGNISI (SEQ IDNO:273) CCGRCVNRRCT Toxin Sequence:Cys-Arg-Xaa3-Ser-Gly-Ser-Asn-Cys-Gly-Asn-Ile-Ser-Ile-Cys-Cys-Gly-Arg-Cys-Val-Asn-Arg-(SEQ ID NO:274) Arg-Cys-Thr-{circumflex over ( )} Name: Sx6.3 Species:striolatus Cloned: Yes DNA Sequence:ACCAAAACCATCATCAAAATGAAACTGACGTGTGTGGTGATCGTCGCCGTTCTGTTC (SEQ IDNO:275) CTGACGGCGTGTCAACTCATCACAGCTGAGGACTCCAGAGGTACACAGAAGCATCGTTCCCTGAGGTCGACTACCAAAGTCTCCAAGTCGACTAGCTGCATGAAAGCCGGGTCTTATTGCGTCGCTACTACGAGAATCTGCTGCGGTTATTGCGCTTATTTCGGCAAAATATGTATTGACTATCCCAAAAACTGATCTTCCCCCTACTGTGCTCTATCCTTTT Translation:MKLTCVVIVAVLFLTACQLITAEDSRGTQKHRSLRSTTKVSKSTSCMKAGSYCVATTRI (SEQ IDNO:276) CCGYCAYFGKICIDYPKN Toxin Sequence:Ser-Thr-Ser-Cys-Met-Lys-Ala-Gly-Ser-Xaa5-Cys-Val-Ala-Thr-Thr-Arg-Ile-Cys-Cys-Gly-Xaa5-(SEQ ID NO:277)Cys-Ala-Xaa5-Phe-Gly-Lys-Ile-Cys-Ile-Asp-Xaa5-Xaa3-Lys-Asn-{circumflexover ( )} Name: Tx6.15 Species: textile Cloned: Yes DNA Sequence:GTTGACTCGGTACTGCACGCCTCATGGAGGACATTGTGGTTATCATAATGACTGCTG (SEQ IDNO:278) CAGTCATCAATGCAATATAAACAGAAATAAATGTGAGTAGCTGATCTGGCATCTGATCTGTGCTCGTCCTTACCTGAGAGTGGTCATGAACCACTCATCACCTACTCCTCTGG AGGCTranslation: LTRYCTPHGGHCGYHNDCCSHQCNINRNKCE (SEQ ID NO:279) ToxinSequence:Xaa5-Cys-Thr-Xaa3-His-Gly-Gly-His-Cys-Gly-Xaa5-His-Asn-Asp-Cys-Cys-Ser-His-Gln-Cys-(SEQ ID NO:280) Asn-Ile-Asn-Arg-Asn-Lys-Cys-Xaa1-{circumflex over ( )}Name: w-Tx Species: textile Isolated: Yes Toxin Sequence:Xaa5-Cys-Thr-Xaa3-Xaa5-Gly-Gly-His-Cys-Gly-Xaa5-His-Asn-Asp-Cys-Cys-Ser-His-Gln-(SEQ ID NO:281) Cys-Asn-Ile-Asn-Arg-Asn-Lys-Cys-Xaa1-{circumflex over( )} Name: C. tulipa w2 Species: tulipa Cloned: Yes DNA Sequence:ACCAAAACCATCATCAAAATGAAACTGACGTGTGTGGTGATCGTCGCCGTGCTGCT (SEQ ID NO:282)CCTGACGGCCTGTCAGCTCATCACAGCTCTGCACTCCAGAGGTACGCAGAAGCATCGTGCCCTGGGGCGGACCACCAAACTCACCTTGTCGACTCGCTGCAAATCACCCGGATCTCCATGTTCACCGACTAGTTATAATTGCTGCTGGTCTTGCAGTCCATACAGAAAAAAATGTAGGGGCTAATCCAGCGCCTGATTTTCCCCCTTCTGTGCTCTATTCCTTTCTGCCTGAGTCCTCCTTACCTGAAAGTGGTCATGAACCACTCATCACCTACTTCTCTGGAGGCTTCGGAGGAGCTACATTGAAATAAAAGCCGCATTGC Translation:MKLTCVVIVAVLLLTACQLITALHSRGTQKHRALGRTTKLTLSTRCKSPGSPCSPTSYNC (SEQ IDNO:283) CWSCSPYRKKCRG Toxin Sequence:Cys-Lys-Ser-Xaa3-Gly-Ser-Xaa3-Cys-Ser-Xaa3-Thr-Ser-Xaa5-Asn-Cys-Cys-Xaa4-Ser-Cys-(SEQ ID NO:284) Ser-Xaa3-Xaa5-Arg-Lys-Lys-Cys-Arg-# Name: w-TVIASpecies: tulipa Cloned: Yes DNA Sequence:ACCAAAACCATCATCAAAATGAAACTGACGTGTGTGGTGATCGTCGCCGTGCTGCT (SEQ ID NO:285)CCTGACGGCCTGTCAGCTCATCACAGCTCTGCACTCCAGAGGTACGCAGAAGCATCGTGCCCTGGGGTCGACCACCAAACTCACCTTGTCGACTCGCTGCTTGTCACCCGGATCTTCATGTTCACCGACTAGTTATAATTGCTGCAGGTCTTGCAATCCATACAGCAGAAAATGTAGGGGCTAATCCAGCGCCTGATCTTCCCCCTTCTGTGCTCTATTCCTTTCTGCCTGAGTCCTCCTTACCTGAAAGTGGTCATGAACCACTCATCACCTACTTCTCTGGAGGCTTCGGAGGAGCTACATTGAAATAAAAGCCGCATTGC Translation:MKLTCVVIVAVLLLTACQLITALHSRGTQKHRALGSTTKLTLSTRCLSPGSSCSPTSYNC (SEQ IDNO:286) CRSCNPYSRKCRG Toxin Sequence:Cys-Leu-Ser-Xaa3-Gly-Ser-Ser-Cys-Ser-Xaa3-Thr-Ser-Xaa5-Asn-Cys-Cys-Arg-Ser-Cys-Asn-(SEQ ID NO:287) Xaa3-Xaa5-Ser-Arg-Lys-Cys-Arg-# Name: Vi6.1 Species:viola Cloned: Yes DNA Sequence:ACCAAAACCATCATCAAAATGAAACTGACGTGTGTGGTGATCGTCGCCGTGCTGCT (SEQ ID NO:288)CCTGACGGCCTGTCAGCTCATTACAGCTGATGACTCCAGAGGTACGCAGTTGCATCGTGCCCTGAGGAAGGCCACCAAACTCCCCGTGTCGACTCGCTGCATTACTTTAGGAACACGATGTAAGGTTCCGAGTCAATGCTGCAGATCTTCTTGCAAGAACGGTCGTTGTGCTCCATCCCCTGAAGAATGGTAAATGTGGCTGATCCAGCGCCTGATCTTCCCCCTTCTGACTGTCTCCGACCTTTTCTGCCTGAGTCCTCCTTACCTGAGAGGTGTCATGAACCACTCATCACCTACTCCCCTGGAAGCTTCAGAGGAGCTACATTGAAATAAAAGCCGCA TTGCTranslation: MKLTCVVIVAVLLLTACQLITADDSRGTQLHRALRKATKLPVSTRCITLGTRCKVPSQC(SEQ ID NO:289) CRSSCKNGRCAPSPEEW Toxin Sequence:Cys-Ile-Thr-Leu-Gly-Thr-Arg-Cys-Lys-Val-Xaa3-Ser-Gln-Cys-Cys-Arg-Ser-Ser-Cys-Lys-Asn-(SEQ ID NO:290) Gly-Arg-Cys-Ala-Xaa3-Ser-Xaa3-Xaa1-Xaa1-Xaa4-{circumflexover ( )} Name: Vi6.2 Species: viola Cloned: Yes DNA Sequence:ACCAAAACCATCATCAAAATGAAACTGACGTGTGTGGTGATCGTCGCCGTGCTGCT (SEQ ID NO:291)CCTGACGGCCTGTCAGCTCATTATAGCTGGGGACTCCAGAGGTACGCAGTTGCATCGTGCCCTGAGGAAGGCCACCAAACTCTCCGTGTCGACTCGCTGCAAGAGTAGAGGATCATCATGTCGTAGGACTTCGTATGACTGCTGCACGGGTTCTTGCAGAAATGGTAAATGTGGCTGATCCAGCGCCTGATCTTCCCCCTTCTGTGCTCCATCCTTTTCTGCCTGAGTCCTCCTTACCTGAGAGTGGGCATGAACCACTCATCACCTACTCCCTGGAAGCTTCAGAGGAGCTACATTGAAATAAAAGCCGCATTGC Translation:MRLTCVVIVAVLLLTACQLIIAGDSRGTQLHRALRKATKLSVSTRCKSRGSSCRRTSYD (SEQ IDNO:292) CCTGSCRNGKCG Toxin Sequence:Cys-Lys-Ser-Arg-Gly-Ser-Ser-Cys-Arg-Arg-Thr-Ser-Xaa5-Asp-Cys-Cys-Thr-Gly-Ser-Cys-Arg-(SEQ ID NO:293) Asn-Gly-Lys-Cys-# Name: Vi6.3 Species: viola Cloned: YesDNA Sequence: ACCAAAACCATCATCAAAATGAAACTGACGTGTGTGGCGATCGTCGCCGTGCTGCT(SEQ ID NO:294) CCTGACGGCCTGTCAGCTCATTACAGCTGAAGACTCCAGAGGTACGCATGAGCATCTTGCCCTGAAGTCGACCTCCAAAGTCTCCAAGTCGACTAGCTGCATGGAAGCCAGATCTTATTGCGGACCTGCTACTACGAAAATCTGCTGCGATTTTTGCAGTCCATTCAGCGATAGATGTATGAACAATCCCAACAATTGATCTTCCCCCTTGTGTGCTCCATCTTTTCTGCCTGAGTCCTCCTTACCTGAGAGTGGTCATGAACCACTCATCACCTACTCCTCTGGAGGCTTCAGAGGAGTTACATTGAAATAAAAGCCGCATGC Translation:MKLTCVAIVAVLLLTACQLITAEDSRGTHEHLALKSTSKVSKSTSCMEARSYCGPATTKI (SEQ IDNO:295) CCDFCSPFSDRCMNNPNN Toxin Sequence:Ser-Thr-Ser-Cys-Met-Xaa1-Ala-Arg-Ser-Xaa5-Cys-Gly-Xaa3-Ala-Thr-Thr-Lys-Ile-Cys-Cys-(SEQ ID NO:296)Asp-Phe-Cys-Ser-Xaa3-Phe-Ser-Asp-Arg-Cys-Met-Asn-Asn-Xaa3-Asn-Asn-{circumflexover ( )} Name: Vi6.4 Species: viola Cloned: Yes DNA Sequence:ACCAAAACCATCATCAAAATGAAACTGACGTGTGTGGTGATCGTCGCCGTGCTGCT (SEQ ID NO:297)CCTGACGGCCTGTCAGCTCATTACAGCTGAGGACTCCAGAGGTACGCAGTTGCATCGTGCCCTGAGGAAGACCACCAAACTCTCCTTGTCGACTCGCTGCAAGGGTCCAGGAGCCATATGTATAAGGATTGCGTATAACTGCTGCAAGTATTCTTGCGGAAATGGTAAATGTGGCTGATCCAGCGCCTGATCTTCCCCCTTGTGTGCTCCATCCTTTTTCTGCCTGAGTCCTCCTTACCTGAGAGTGGTCATGAACCACTCATCACCTACTCCTCTGGAGGCTTCAGAGGAGCTACATTGAAATAAAAGCCGCATGC Translation:MKLTCVVIVAVLLLTACQLITAEDSRGTQLHRALRKTTKLSLSTRCKGPGAICIRIAYNC (SEQ IDNO:298) CKYSCGNGKCG Toxin Sequence:Cys-Lys-Gly-Xaa3-Gly-Ala-Ile-Cys-Ile-Arg-Ile-Ala-Xaa5-Asn-Cys-Cys-Lys-Xaa5-Ser-Cys-(SEQ ID NO:299) Gly-Asn-Gly-Lys-Cys-# Name: Vi6.5 Species: viola Cloned:Yes DNA Sequence:ACCAAAACCATCATCAAAATGAAACTGACGTGTGTGGTGATCGTCGCCGTGCTGTTC (SEQ IDNO:300) CTGACGGCCTGTCAATTCATCACAGCTGATGACTCCAGAAGTACGCAGAAGCATCGTGCCCTGAGGTCGACCACCAAACACTTTATGTTGACTTGGTACTGCACGCCTTATGGAGGACATTGTGGTTATTATAATGACTGCTGCAGTCATCAATGCAATATAAACAGAAATAAATGTGAGTAGCTGATCCGGCATCTGATCTGTGCTCGCCCTAACCTGAGAGTGGTCATGAACCACTCATCATCTACTCCTCTGGAGGCTTCAGAGGAGCTACATGGAAATA AAAGCCGCATTGCTranslation: MKLTCVVIVAVLFLTACQFITADDSRSTQKHRALRSTTKHFMLTWYCTPYGGHCGYYN(SEQ ID NO:301) DCCSHQCNINRNKCE Toxin Sequence:Xaa5-Cys-Thr-Xaa3-Xaa5-Gly-Gly-His-Cys-Gly-Xaa5-Xaa5-Asn-Asp-Cys-Cys-Ser-His-Gln-(SEQ ID NO:302) Cys-Asn-Ile-Asn-Arg-Asn-Lys-Cys-Xaa1-{circumflex over( )} Name: Pu6.4 Species: pulicarius Cloned: Yes DNA Sequence:GGATCCATGAAACTGACGTGCGTGGTGATTATCGCCGTGCTGTTCCTGACGGCCTGT (SEQ IDNO:303) CAACTCATTACAGCTGAGACTTACTCCAGAGGTAAGCAGATGCACCGTGCTCTGAGGTCAACTGACAAAAACTCCAAGTTGACCAGGGAATGCACACCTCCAGATGGAGCTTGTGGTTTACCTACACACTGCTGCGGGTTTTGCGATATGGCAAACAACAGATGTCTGTAAAGCGTCTGATATTCCCCTTCTGTGCTCTATCCTCTTTGGCCTGAGTCATCCATACC TGTGCTCGAGTranslation: MKLTCVVIIAVLFLTACQLITAETYSRGKQMHRALRSTDKNSKLTRECTPPDGACGLPT(SEQ ID NO:304) HCCGFCDMANNRCL Toxin Sequence:Xaa1-Cys-Thr-Xaa3-Xaa3-Asp-Gly-Ala-Cys-Gly-Leu-Xaa3-Thr-His-Cys-Cys-Gly-Phe-Cys-(SEQ ID NO:305) Asp-Met-Ala-Asn-Arg-Cys-Leu-{circumflex over ( )} Name:Pu6.6 Species: pulicarius Cloned: Yes DNA Sequence:GGATCCATGAAACTGACGTGCGTGGTGATTATCGCCGTGCTGTTCCTGACGGCCTGT (SEQ IDNO:306) CAACTCATTACAGCTGAGACTTACTCCAGAGGTAAGCAGATGCACCGTGCTCTGAGGTCAACTGACAAAAACTCCCAGTTGACCAGGGAATGCACACCTCCAGGTGGAGCTTGTGGTTTACCTACACACTGCTGCGGGTTTTGCGATATGGCAAACAACAGATGTCTGTAAAGCGTCTGATATTCCCCTTCTGTGCTCTATCCTCTTTGGCCTGAGTCATCCATACC TGTGCTCGAGTranslation: MKLTCVVIIAVLFLTACQLITAETYSRGKQMHRALRSTDKNSQLTRECTPPGGACGLPT(SEQ ID NO:307) HCCGFCDMANNRCL Toxin Sequence:Xaa1-Cys-Thr-Xaa3-Xaa3-Gly-Gly-Ala-Cys-Gly-Leu-Xaa3-Thr-His-Cys-Cys-Gly-Phe-Cys-(SEQ ID NO:308) Asp-Met-Ala-Asn-Asn-Arg-Cys-Leu-{circumflex over ( )}Name: Ra6.4 Species: rattus Cloned: Yes DNA Sequence:GGATCCATGAAACTGACGTGTGTGGTGATCATCGCCGTGCTGTTCCTGGCAGCCTGT (SEQ IDNO:309) CAACCTGTTACAACTGAGACTTTCTCCAGAGGTAAGGAGAAGCGTCGTGCTCTGAGGTCAACTGACGGCAACTCCCGGTTGACCAGGGCATGCACGCCTGAAGGTGGAGCCTGTAGTAGTGGGCGTCACTGCTGCGGCTTTTGCGATAACGTGTCCCACACGTGCTATGGTGAAACACCATCTCTCCACTGATGTTTCCCCTTCTGTGCTCTATCTTCTTTTGCCTGAGTCATCCATACCTGTGCTCGAG Translation:MKLTCVVIIAVLFLAACQPVTTETFSRGKEKRRALRSTDGNSRLTRACTPEGGACSSGR (SEQ IDNO:310) HCCGFCDNVSHTCYGETPSLH Toxin Sequence:Ala-Cys-Thr-Xaa3-Xaa1-Gly-Gly-Ala-Cys-Ser-Ser-Gly-Arg-His-Cys-Cys-Gly-Phe-Cys-Asp-(SEQ ID NO:311)Asn-Val-Ser-His-Thr-Cys-Xaa5-Gly-Xaa1-Thr-Xaa3-Ser-Leu-His-{circumflexover ( )} Name: Sm6.7 Species: stercusmuscarum Cloned: Yes DNA Sequence:AGATCCATGAAACTGACGTGCGTGGTGATCGTCGCCGTGCTGCTCCTGACGGCCTGT (SEQ IDNO:312) CAACTCATCACAGCTGATGACTCCAGAGGTACGCAGGAGCATCGTGCCCTGAGGTCGGACACCAAACTCCCCATATCGACTCGCTGCAAGGGTAAAGGAGCATCATGTCATAAGACTATGTATGACTGCTGCAGCGGTTCCTGCACCAGAGGTAGATGTGGCTGATCCAGCGCCTGATCTTCCCCCTTCTGTGCTCTATCCTTTTCTGCCTGAGTCATCATACCTGTGCTCGAGCGTTACTAGTGGATCCGAGCTCGGTACCAAGCTTGGCGTAATCATAAA ANCTranslation: MKLTCVVIVAVLLLTACQLITADDSRGTQEHRALRSDTKLPISTRCKGKGASCHKTMYD(SEQ ID NO:313) CCSGSCTRGRCG Toxin Sequence:Cys-Lys-Gly-Lys-Gly-Ala-Ser-Cys-His-Lys-Thr-Met-Xaa5-Asp-Cys-Cys-Ser-Gly-Ser-Cys-Thr-(SEQ ID NO:314) Arg-Gly-Arg-Cys-# Xaa1 = Glu or γ-Carboxy Glu Xaa2 = Glnor pyroGlu Xaa3 = Pro or Hydroxy Pro Xaa4 = Trp or Bromo Trp Xaa5 = Tyr,¹²⁵I-Tyr, mono-iodo-Tyr or di-iodo-Tyr or O-sulpho-Tyr or O-Phospho-Tyr{circumflex over ( )} = Free-carboxyl C-term or Amidated C-term,preferably Free-carboxyl # = Free-carboxyl C-term or Amidated C-term,preferably Amidated

[0097] TABLE 2 +HZ,40 Alignment of ω-Conopeptides (SEQ ID NO:) Ar6.10(F170) ---QCSANGGSC-TRHFH---CCSLYCNKDSSVCVATSYP{circumflex over ( )}(315) Ar6.2 (F074) ---TCNTPTEYC-TLHRH---CCSGYCHKTIQACS{circumflex over( )} (316) Ar6.3 ---QCTPNGGSC-SRHFH---CCSLYCNKSTGVCIATSYP{circumflexover ( )} (317) Ar6.4 (F009)---TCNTPTEYC-TLHQH---CCSGYCHKTIQACS{circumflex over ( )} (318) Ar6.6(F069) ---ECTPPGGACGLPT-H---CC-GFCDTANNRCL{circumflex over ( )} (319)Ar6.7 (F073) ---TCNTPTEYC-TLHQH---CCSGHCHKTIQACA{circumflex over ( )}(320) Ar6.8 (F169) ---QCSPIGGYC-TLHIH---CCSNHCIKPIGRCVAT{circumflex over( )} (321) Ar6.9 (F171) ---QCLPNGGYC-TLHIH---CCSDHCIKPIDRCVAT{circumflexover ( )} (322) Ay6.1 (A653) ----CKGKGKPCSRISYN---CCTGSCRS--GKC# (323)Ay6.2 (A654) ----CMEAGSYCG-STTR--ICC-GFCAYFGKKCIDYPSN{circumflex over( )} (324) Ay6.3 (J419) ----CKAKGKPCSRIAYN---CCTGSCRS--GKC# (325) Ay6.4----CASYGKPCGIDN-D---CCNA-CDPGRNICT{circumflex over ( )} (326) Bu6.1-STSCMEAGSYCGPATTK--ICC-DFCSPFSDRCMNNPNN{circumflex over ( )} (327)Bu6.2 ----CITPGTRCKVPS-Q---CCRGPCKNGR--CTPSPSEW{circumflex over ( )}(328) Bu6.3 ----CATYGKPCGIQN-D---CC-NTCDPARRTCT{circumflex over ( )}(329) Bu6.4 ----CKGPGASCIRIAYN---CCKYSCRN---GKC# (330) Bu6.5-STSCMAAGSYCGPATTN--ICC-DFCSPFSDRCMKKPNN{circumflex over ( )} (331)Bu6.6 ----CKSKGSSCHRTSYD---CCTGSCRN--GRC# (332) C6.1----CKSTGASCRRTSYD---CCTGSCRS--GRC# (333) C6.4----CQGRGASCRKTMYN---CCSGSCN--RGSC# (334) C6.5----CLPAGESCLFSRIR---CC-GTCSSVLKSCVS{circumflex over ( )} (335) C6.6----CQGRGGPCTKAVFN---CCSGSCN--RGRC# (336) C6.7----CATYGKPCGIQN-D---CC-NTCDPARKTCT{circumflex over ( )} (337) C6.8----CRGRGGPCTKAMFN---CCSGSCN--RGRC# (338) Ca6.4 (F168)---QCSANGGSC-TRHFH---CCSLYCNKDSSVCVATSYP{circumflex over ( )} (339)Cn6.1 ----CASYGKPCGIDN-D---CC-NTCDPARKTCT{circumflex over ( )} (340)Cn6.2 (I583) ----CKGTGKPCSRIAYN---CCTGSCRS--GKC# (341) Cn6.3-ATDCIEAGNYCGPTVMK--ICC-GFCSPYSKICMNYPQN{circumflex over ( )} (342)Cn6.4 ----CKGKGASCTRLMYD---CCHGSCSSSKGRC# (343) Cn6.5 (I590)----CKGKGASCHRTSYD---CCTGSCN--RGKC# (344) Cn6.6 (I584)----CASYGKPCGIYN-D---CC-NTCDPARKTCT{circumflex over ( )} (345) Cn6.7(J409) ----CKGTGKPCSRVAYN---CCTGSCRS--GKC# (346) Cn6.8 (J407)-STSCMKAGSYCR-STTR--TCC-GYCAYFGKFCIDFPSN{circumflex over ( )} (347)Cr6.1 ----CKGKGASCRKTMYN---CCSGSCSN--GRC# (348) Cr6.2-STSCMEAGSYCR-STTR--TCC-GYCSYFSKKCIDFPSN{circumflex over ( )} (349)Cr6.3 ----CKSKGAKCSRLMYD---CCSGSCSRYSGRC# (350) Cr6.4-STGCMKAGSYCR-STTR--TCC-GYCAYFGKKCIDYPSN{circumflex over ( )} (351)Da6.8 ---SCTPPGGPCGYYN-D---CCSHQCNISRNKCE{circumflex over ( )} (352)Di6.1 ----CEDOGEOCGSDH-S---CCGGSCN--HNVCA{circumflex over ( )} (353)E6.2 ---PCKPKGRKCFPHQKD---CCNKTCT--RSKCP{circumflex over ( )} (354) E6.3---ACWSSGTPCGTDS-L---CCGG-CNVSKSKCN{circumflex over ( )} (355) G6.1(J420) ----CKSPGSSCSPTSYN---CCR-SCNPYAKRCY# (356) G6.2 (J423)----CKSPGTPCSRGMRD---CCT-PCLLYSNKC-R--RY{circumflex over ( )} (357) J410----CLSPGSRCHKTMRN---CCT-SCSSYKGKCRP--RK{circumflex over ( )} (358) J411----CKPPGRKCLNRKNE---CCSKFCNEHLHMC# (359) J413----CKPPRRKCLKIKDK---CC-NFCNTHLNMC# (360) J414----CAGPGTIC--PNRV---CC-GYCSKRTHLCHS---RT# (361) La6.1---KCWPSGSYCRANS-K---CCSG-CDRNRNKCY{circumflex over ( )} (362) La6.2----CLPPGSYCK-ATTE--VCCS-SCLQFAQIC-----S# (363) L6.1----CKSPGSPCSVTSYN---CCT-FCSSYTKKCRA--SL{circumflex over ( )} (364) L6.2----CAGPGAIC--PNRV---CC-GYCSKRTHLCHS---RT# (365) L6.3---ACWSSGTPCGTDS-L---CCGG-CNVSKSKCN{circumflex over ( )} (366) L6.4---KCWSPGTYCRAHS-K---CCRG-CDQNRNKCY{circumflex over ( )} (367) La6.3----CKSPGSSCSVSMRN---CCT-SCNSRTKKCTR--R# (368) La6.4---TCWPSGTACGIDS-N---CCSG-CNVSRSKCN{circumflex over ( )} (369) La6.5---KCWPSGSYCRANS-K---CCSG-CDRNRSKCN{circumflex over ( )} (370) Lp6.1(JG4) SLFECAPSGGRCGFLK-S---CCEGYCDGESTSCVSGPYSI{circumflex over ( )}(371) Lp6.2 (JG5) WPLDCTAPSQPCGYFP-R---CCG-HCDV-RRVCTS# (372) Lp6.3(JG7) ----CMSPGGICGDFG-D---CCE-ICNV-YGICVSDLPGI{circumflex over ( )}(373) Lp6.4 (JG15) ---YCAPPGGACGFFD-H---CC-GYCETFYNTC-R{circumflex over( )} (374) M6.1 ----CKGTGKPCSRIAYN---CCTGSCRS-GKC# (375) M6.2----CASYGKPCGIYN-D---CC-NTCDPARKTCT{circumflex over ( )} (376) Mi6.1(F157) ----CNDRGGGC-SQHPH---CCGGTCNKLIGVCL{circumflex over ( )} (377)Mn6.1 ----CKSTGKSCSRIAYN---CCTGSCRS--GKC# (378) Mn6.2----CKGKGSSCSRTMYN---CCTGSCN--RGKC# (379) O6.1-SPPCMKGGSSCR-GTTG--VCC-GFCSDFGYKCRDYPQN{circumflex over ( )} (380) O6.2----CLPDGTSCLFSRIR---CC-GTCSSILKSCVS{circumflex over ( )} (381) P6.1---OCKTOGRKCFOHQKD---CCGRACI--ITICP{circumflex over ( )} (382) P6.2---SCKLOGAYCNAXDYD---CCLR-CKV-GGTC# (383) P6.3---PCKKTGRKCFPHQKD---CCGRACI--ITICP{circumflex over ( )} (384) Pu6.2(JG28) ---QCSPNGGSC-SRHFH---CCSLYCNKNTGVCIAT{circumflex over ( )} (385)Pu6.4 (AA678) ---ECTPPDGACGLPT-H---CC-GFCDMANNRCL{circumflex over ( )}(386) Pu6.6 (AAG81) ---ECTPPGGACGLPT-H---CC-GFCDMANNRCL{circumflex over( )} (387) R6.1 --HGCKPLKRRCFNDKE----CCSKFCNSVRKQC# (388) R6.2--RGCKPLKRRCFNDKE----CCSKFCNSVRNQC# (389) Ra6.1 (F206)----CNARNDGC-SQHSQ---CCSGSCNKTAGVCL{circumflex over ( )} (390) Ra6.2(F205) ----CNARNSGC-SQHPQ---CCSGSCNKTAGVCL{circumflex over ( )} (392)Ra6.3 (F207) ----CNARNSGC-SQHPQ---CCSGSCNKTLGVCL{circumflex over ( )}(393) Ra6.4 (AA688)---ACTPEGGACSSGR-H---CC-GFCDNVSHTCYGETPSLH{circumflex over ( )} (394)S6.1 -ATDCIEAGNYCGPTVMK--ICC-GFCSPYSKICMNYPKN{circumflex over ( )} (395)S6.2 ----CKLKGQSCRRTMYD---CCSGSCGR-RGKC# (396) S6.3----CKAAGKSCSRIAYN---CCTGSCRS--GKC# (397) S6.6----CESYGKPCGIYN-D---CC-NACDPAKKTCT{circumflex over ( )} (398) Sm6.1(J428) ----CKSKGAKCSRLMYD---CCSGSCSGYTGRC# (399) Sm6.2-TTSCMQAGSYCG-STTR--ICC-GYCAYFGKKCIDYPSN{circumflex over ( )} (400)Sm6.3 (J429) ----CASYGKPCGIDN-D---CC-NACDPARNICT{circumflex over ( )}(401) Sm6.4 (J431) ----CVSYGKPCGIDN-D---CC-NACDPARNICT{circumflex over( )} (402) Sm6.7 (AAG89) ----CKGKGASCHKTMYD---CCSGSCTRG--RC# (403) Sx6.1----CKGKGASCLRTAYD---CCTGSCN--RGRC# (404) Sx6.2----CRPSGSNCGNIS-I---CCGR-CVN--RRCT{circumflex over ( )} (405) Sx6.3-STSCMKAGSYCV-ATTR--ICC-GYCAYFGKICIDYPKN{circumflex over ( )} (406)Tx6.15 ---YCTPHGGHC-GYHND---CCSHQCNINRNKCE{circumflex over ( )} (407)Vi6.1 ----CITLGTRCKVPS-Q---CCRSSCKN--GRCAPSPEEW{circumflex over ( )}(408) Vi6.2 ----CKSRGSSCRRTSYD---CCTGSCRN--GKC# (409) Vi6.3-STSCMEARSYCGPATTK--ICC-DFCSPFSDRCMNNPNN{circumflex over ( )} (410)Vi6.4 ----CKGPGAICIRIAYN---CCKYSCGN--GKC# (411) Vi6.5---YCTPYGGHCGYYN-D---CCSHQCNINRNKCE{circumflex over ( )} (412) ω-Tx----CTPYGGHCGYNH-D---CCSHQCNINRNKCE{circumflex over ( )} (413) C. tulipaω2 ----CKSWGSOCSOTSTN---CCW-SCSPYRKKC-R# (414)

Example 3 In vivo Activity of ω-Conopeptide Frings Audiogenic SeizureSusceptible Mice

[0098] In vivo anticonvulsant activity of ω-conopeptides is analyzed inFrings audiogenic seizure susceptible mice as described by White et al.(1992). The ω-conopeptides are found to have anticonvulsant activity inthis assay.

Example 4 In vivo Activity of ω-Conopeotides in CF No. 1 Mice

[0099] In vivo anticonvulsant activity of o)conopeptides is analyzed inCF No. 1 mice as described by White et al. (1995), using the maximalelectroshock, subcutaneous pentylenetetrazole (Metrazol) seizurethreshold and threshold tonic extension test. ω-Conopeptides are foundto have anticonvulsant activity.

Example 5 In Vivo Activity of ω-Conopeptides inPentylenetetrazole-Induced Threshold Seizure Model

[0100] The in vivo activity of ω-conopeptides is analyzed using timedintravenous infusion of pentylenetetrazole (White et al., 1995). At timeto peak effect, the convulsant solution (0.5% pentylenetetrazole in 0.9%saline containing 10 U.S.P. units/ml heparin sodium) is infused into thetail vein at a constant rate of 0.34 ml/min. The time in seconds fromthe start of the infusion to the appearance of the first twitch and theonset of clonus is recorded for each drug treated or control animal. Thetimes to each endpoint are converted to mg/kg of pentylenetetrazole foreach mouse, and mean and standard error of the mean are calculated. Itis found that ω-conopeptides elevate the i.v. pentylenetetrazole seizurethreshold.

Example 6 In vivo Activity of ω-Conopeptides in Pain Models

[0101] The anti-pain activity of ω-conopeptides is shown in severalanimal models.

[0102] These models include the nerve injury model (Chaplan, et al.,1997), the nocioceptive response to s.c. formalin injection in rats(Codene, 1993) and an NMDA-induced persistent pain model (Liu, et al.,1997). In each of these models it is seen that the ω-conopeptides andω-conopeptides derivatives have analgesic properties.

[0103] More specifically, this study evaluates the effect of intrathecaladministration of ω-conopeptides in mice models of nocioceptive andneuropathic pain. For nocioceptive pain, the effect of theω-conopeptides is studied in two different tests of inflammatory pain.The first is the formalin test, ideal because it produces a relativelyshort-lived, but reliable pain behavior that is readily quantified.There are two phases of pain behavior, the second of which is presumedto result largely from formalin-evoked inflammation of the hind paw. Anω-conopeptide is administered 10 minutes prior to injection of formalin.The number of flinches and/or the duration of licking produced by theinjection is monitored. Since the first phase is presumed to be due todirect activation of primary afferents, and thus less dependent on longterm changes in the spinal cord, ω-conopeptides are presumed to havegreatest effect on the magnitude of pain behavior in the second phase.

[0104] The mechanical and thermal thresholds in animals that received aninjection of complete Freund's adjuvant into the hind paw are alsostudied. This produces a localized inflammation including swelling ofthe hind paw and a profound decrease in mechanical and thermalthresholds, that are detected within 24 hours after injection. Thechanges in thresholds in rats that receive ω-conopeptides are comparedwith those of rats that receive vehicle intrathecal injections.

[0105] An important issue is whether the drugs are effective whenadministered after the pain model has been established, or whether theyare effective only if used as a pretreatment. Clearly, the clinical needis for drugs that are effective after the pain has developed. To addressthis issue, animals are studied in which ω-conopeptides are administeredrepeatedly, after the inflammation (CFA) or nerve injury has beenestablished. In these experiments, an ω-conopeptide is injected daily bythe intrathecal (i.t.) route. The mechanical and thermal thresholds(measured, respectively, with von Frey hairs in freely moving animalsand with the Hargreave's test, also in freely moving animals) arerepeated for a 2 to 4 week period after the injury is induced and thechanges in pain measured monitored over time.

Example 7 Effect of -Conotoxins in a Pain Model

[0106] Analgesic activity of ω-conotoxins is also tested in pain modelsas follows.

[0107] Persistent pain (formalin test). Intrathecal (it) drug injectionsare performed as described by Hylden and Wilcox (1980). An ω-conopeptideor vehicle is administered in a volume of 5 1. Fifteen minutes after thei.t. injection, the right hindpaw is injected with 20 l of 5% formalin.Animals are placed in clear plexiglass cylinders backed by mirrors tofacilitate observation. Animals are closely observed for 2 minutes per 5minute period, and the amount of time the animal spent licking theinjected paw is recorded in this manner for a total of 45-50 minutes.Results are expressed as licking time in seconds per five minutes. Atthe end of the experiment, all animals are placed on an acceleratingrotorod and the latency to first fall was recorded. ω-Conopeptides arefound to be active in this model which is predictive of efficacy fortreating neuropathic pain.

[0108] Acute pain (tail-flick). An ω-conopeptide or saline isadministered intrathecally (i.t.) according to the method of Hylden andWilcox (1980) in a constant volume of 5 μl. Mice are gently wrapped in atowel with the tail exposed. At various time-points following the i.t.injection, the tail is dipped in a water bath maintained at 54 C. andthe time to a vigorous tail withdrawal is recorded. If there is nowithdrawal by 8 seconds, the tail is removed to avoid tissue damage.

[0109] Neuropathic pain. The partial sciatic nerve ligation model isused to assess the efficacy of Marl in neuropathic pain. Nerve injury isproduced according to the methods of Malmberg and Basbaum (1998).Animals are anesthetized with a ketamine/xylazine solution, the sciaticnerve is exposed and tightly ligated with 8-0 silk suture around ⅓ to ½of the nerve. In sham-operated mice the nerve is exposed, but notligated. Animals are allowed to recover for at least 1 week beforetesting is performed. On the testing day, mice are placed in plexiglasscylinders on a wire mesh frame and allowed to habituate for at least 60minutes. Mechanical allodynia is assessed with calibrated von Freyfilaments using the up-down method as described by Chaplan et al.(1994), and the 50% withdrawal threshold is calculated. Animals that didnot respond to any of the filaments in the series are assigned a maximalvalue of 3.6 grams, which is the filament that typically lifted thehindlimb without bending, and corresponds to approximately {fraction(1/10)} the animal's body weight.

[0110] The data obtained demonstrate that ω-conopeptides have potentanalgesic properties in three commonly used models of pain: acute,persistent/inflammatory and neuropathic pain models.

Example 8 Calcium-Channel Antagonist Activity

[0111] Inhibition of Ionic Currents

[0112] Ionic currents through calcium channels are examined in cellsthat are voltage-clamped by a single patch-clamp electrode. Thesewhole-cell patch-clamp studies are performed mainly on N1E115 mouseneuroblastoma cells, although a variety of cell types, including humanneuroblastoma cell line IMR-32, are also examined.

[0113] Most measurements are obtained using a bath saline that allowedexamination of the calcium currents in the absence of other ioniccurrents. These solutions contained 80 mM NMDG (as a sodiumreplacement), 30 mM TEACl (to block potassium currents), 10 mM BaCl₂ (asa charge-carrier through the calcium channels), and 10 mM HEPES at pH7.3. Some solutions also contained 2 mM quinidine (to block potassiumcurrents) and 3 μM tetrodotoxin (to block sodium currents). Normal bathsaline is (mnM): 140 NaCl, 10 glucose, 3 KCl, 2 CaCl₂, 1 MgCl₂, 10 mMHEPES pH 7.3. Intracellular solutions contained (mM): 150 CsCl, 0.5CaCl₂, 5 EGTA, 5 MgCl₂, 2 K₂ATP at pH 7.3-7.4. Bath saline and allinternal solutions are filtered before use.

[0114] Pipets are made from Coming 7052 glass (Garner Glass Company,Claremont, Calif. 91711), coated with Sylgard (Dow Coming, Midland,Mich. 48640) and fire-polished before use. Bubble numbers are typically5 to 6, with pipet resistances typically 2-5 MOhms.

[0115] Corning 8161, Kimble, and other glasses are also used withoutnoticeable effect on the calcium currents observed.

[0116] Recordings are carried out at room temperature with an Axopatch1-C amplifier (Axon Instruments, Foster City, Calif. 94404) and analyzedwith pCLAMP software (Axon Instruments). Data are filtered at 1000 Hzfor a typical sampling rate of 0.1 kHz; in all cases data are filteredat a frequency at most ⅕ of the sampling rate to avoid biasing. Data arecollected on-line by the software. Analysis is performed on-screen withprint-out via a Hewlett-Packard LaserJet Printer (Hewlett-Packard, PaloAlto, Calif. 94306).

[0117] The typical experiment is conducted as follows: after sealformation followed by series resistance compensation and capacitativetransient cancellation, a voltage clamp protocol is performed whereinthe cell potential is stepped from the holding potential (typically −100mV) to test potentials that ranged from −60 mV to +20 mV in 10 mVincrements. The cell is held at the holding potential for 5 secondsbetween pulses. Protocols starting from other holding potentials usuallycovered the same range of test potentials. ω-Conopeptides are found tohave calcium channel blocking activity in such cell lines.

[0118] It will be appreciated that the methods and compositions of theinstant invention can be incorporated in the form of a variety ofembodiments, only a few of which are disclosed herein. It will beapparent to the artisan that other embodiments exist and do not departfrom the spirit of the invention. Thus, the described embodiments areillustrative and should not be construed as restrictive.

BIBLIOGRAPHY

[0119] Abiko, H. et al. (1986). Brain Res. 38:328-335.

[0120] Aldrete, J. A. et al. (1979). Crit. Care Med. 7:466-470.

[0121] Barnay, G. et al. (2000). J. Med. Chem.

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1 413 1 318 DNA Unknown unknown Conus species 1 ggatccatga aactgacgtgcatggtgatc gtcgccgtgc tgctcctgac ggcctgtcaa 60 ctcatcacag ctgatgactccagaggtacg cagaagcatc atgccctgag gtcgaccacc 120 aatttctcca cgttgactcgtcgctgcctt tctcccggat cacgatgtca taagacaatg 180 cgtaactgct gcacttcatgctcttcatac aaagggaaat gtcggcctcg aaaatgaacc 240 actcatcacc tactcctctggaggcctcag aggaattaca ttgaaataaa agccgcatta 300 caaaaaaaaa aaaaaaaa 3182 76 PRT Unknown unknown Conus species 2 Met Lys Leu Thr Cys Met Val IleVal Ala Val Leu Leu Leu Thr Ala 1 5 10 15 Cys Gln Leu Ile Thr Ala AspAsp Ser Arg Gly Thr Gln Lys His His 20 25 30 Ala Leu Arg Ser Thr Thr AsnPhe Ser Thr Leu Thr Arg Arg Cys Leu 35 40 45 Ser Pro Gly Ser Arg Cys HisLys Thr Met Arg Asn Cys Cys Thr Ser 50 55 60 Cys Ser Ser Tyr Lys Gly LysCys Arg Pro Arg Lys 65 70 75 3 30 PRT Unknown unknown Conus species 3Cys Leu Ser Xaa Gly Ser Arg Cys His Lys Thr Met Arg Asn Cys Cys 1 5 1015 Thr Ser Cys Ser Ser Xaa Lys Gly Lys Cys Arg Xaa Arg Lys 20 25 30 4283 DNA Unknown unknown Conus species 4 ggatccatga aactgacgtg cgtggtgatcgtcgccgtgc tgctcctgac ggtctgtcaa 60 ctcatcacag ctgatgactc cagaggtacgcagaagcatc atgccctgag gtcgaccacc 120 aatttctcca cgtcgactcg tcgctgcaaacctcccggaa gaaaatgtct gaatagaaag 180 aatgaatgct gcagcaagtt ttgcaatgaacacctacata tgtgtggata aatggctaaa 240 aactgaataa aagccgcatt gcaaaaaaaaaaaaaaaaaa aaa 283 5 74 PRT Unknown unknown Conus species 5 Met Lys LeuThr Cys Val Val Ile Val Ala Val Leu Leu Leu Thr Val 1 5 10 15 Cys GlnLeu Ile Thr Ala Asp Asp Ser Arg Gly Thr Gln Lys His His 20 25 30 Ala LeuArg Ser Thr Thr Asn Phe Ser Thr Ser Thr Arg Arg Cys Lys 35 40 45 Pro ProGly Arg Lys Cys Leu Asn Arg Lys Asn Glu Cys Cys Ser Lys 50 55 60 Phe CysAsn Glu His Leu His Met Cys Gly 65 70 6 27 PRT Unknown unknown Conusspecies 6 Cys Lys Xaa Xaa Gly Arg Lys Cys Leu Asn Arg Lys Asn Xaa CysCys 1 5 10 15 Ser Lys Phe Cys Asn Xaa His Leu His Met Cys 20 25 7 275DNA Unknown unknown Conus species 7 ggatccatga aactgacgtg cgtggtgatcgtcgccgtgc tgctcctgac ggcctgtcaa 60 ctcgtcacag ctgatggctc cagaggtatgcagaagcatt atgccctgag gtcgaccacc 120 aatctctcca tatcgtctcg ctgcaaacctcccagaagaa aatgtctgaa gattaaggat 180 aaatgctgca acttttgcaa tacacacctaaatatgtgtg gataaatggc taaaaactga 240 ataaaagccg cattgcaaaa aaaaaaaaaaaaaaa 275 8 72 PRT Unknown unknown Conus species 8 Met Lys Leu Thr CysVal Val Ile Val Ala Val Leu Leu Leu Thr Ala 1 5 10 15 Cys Gln Leu ValThr Ala Asp Gly Ser Arg Gly Met Gln Lys His Tyr 20 25 30 Ala Leu Arg SerThr Thr Asn Leu Ser Ile Ser Ser Arg Cys Lys Pro 35 40 45 Pro Arg Arg LysCys Leu Lys Ile Lys Asp Lys Cys Cys Asn Phe Cys 50 55 60 Asn Thr His LeuAsn Met Cys Gly 65 70 9 26 PRT Unknown unknown Conus species 9 Cys LysXaa Xaa Arg Arg Lys Cys Leu Lys Ile Lys Asp Lys Cys Cys 1 5 10 15 AsnPhe Cys Asn Thr His Leu Asn Met Cys 20 25 10 377 DNA Unknown unknownConus species 10 ggatccatga aactgacgtg tgtggtgatc gtcgccgtgc tgctcctgatggcctgtcaa 60 ctcgtcacag ctgatggctc cagaggtatg cacaagcatt atgccctgaggtcgaccacc 120 aaactctcca tgtcgactcg ctgcgcaggt ccaggaacaa tttgtcctaatagggtatgc 180 tgcggttatt gcagtaaaag aacacatcta tgtcattcgc gaactggctgatcttccccc 240 ttctgcgctc catccttttc tgcctgagtc ctccatacct gagaatggtcatgaaccact 300 caacacctac tcctctggag ggcctcagaa gagctacatt gaaataaaagccgcattaca 360 aaaaaaaaaa aaaaaaa 377 11 74 PRT Unknown unknown Conusspecies 11 Met Lys Leu Thr Cys Val Val Ile Val Ala Val Leu Leu Leu MetAla 1 5 10 15 Cys Gln Leu Val Thr Ala Asp Gly Ser Arg Gly Met His LysHis Tyr 20 25 30 Ala Leu Arg Ser Thr Thr Lys Leu Ser Met Ser Thr Arg CysAla Gly 35 40 45 Pro Gly Thr Ile Cys Pro Asn Arg Val Cys Cys Gly Tyr CysSer Lys 50 55 60 Arg Thr His Leu Cys His Ser Arg Thr Gly 65 70 12 28 PRTUnknown unknown Conus species 12 Cys Ala Gly Xaa Gly Thr Ile Cys Xaa AsnArg Val Cys Cys Gly Xaa 1 5 10 15 Cys Ser Lys Arg Thr His Leu Cys HisSer Arg Thr 20 25 13 323 DNA Conus arenatus 13 ggatccatga aactgacgtgcatggtgatc atcgccgtgc tgttcctgac ggcctgtcaa 60 ctcattacag gtgagcagaaggaccatgct ctgaggtcaa ctgacaaaaa ctccaagttg 120 actaggcagt gctcggctaacggtggatct tgtactcgtc attttcactg ctgcagcctc 180 tattgcaata aagattccagtgtatgtgtg gcaacctcat acccgtgagt ggccatgaac 240 ccctcaatac cctctcctctggaggcttca gaggaactgc attgaaataa aaccgcattg 300 caataaaaaa aaaaaaaaaaaaa 323 14 73 PRT Conus arenatus 14 Met Lys Leu Thr Cys Met Val Ile IleAla Val Leu Phe Leu Thr Ala 1 5 10 15 Cys Gln Leu Ile Thr Gly Glu GlnLys Asp His Ala Leu Arg Ser Thr 20 25 30 Asp Lys Asn Ser Lys Leu Thr ArgGln Cys Ser Ala Asn Gly Gly Ser 35 40 45 Cys Thr Arg His Phe His Cys CysSer Leu Tyr Cys Asn Lys Asp Ser 50 55 60 Ser Val Cys Val Ala Thr Ser TyrPro 65 70 15 33 PRT Conus arenatus PEPTIDE (1)..(33) Xaa at residue 1 isGln or pyro-Glu; Xaa at residue 33 is Pro or Hyp; Xaa at residue 19 and32 is Tyr, 125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr orO-phospho-Tyr 15 Xaa Cys Ser Ala Asn Gly Gly Ser Cys Thr Arg His Phe HisCys Cys 1 5 10 15 Ser Leu Xaa Cys Asn Lys Asp Ser Ser Val Cys Val AlaThr Ser Xaa 20 25 30 Xaa 16 326 DNA Conus arenatus 16 accaaaaccatcatcaaaat gaaactgacg tgcgtgttga ttatcgccgt gctgttcctg 60 acggcctgtcaactcattac agctgagact tactccagag gtgagcagaa gcaccatgct 120 ctgaggtcaactgacagaaa ctccaagttg accaggacat gcaacactcc cactgaatat 180 tgtactttgcatcgacactg ctgcagcggc tactgccata aaacaatcca ggcatgttca 240 taataccggtgagtggtcat gaaccactca ataccctctc ctctggaggc ttcagaggaa 300 ctgcattgaaataaaagccg cattgc 326 17 74 PRT Conus arenatus 17 Met Lys Leu Thr CysVal Leu Ile Ile Ala Val Leu Phe Leu Thr Ala 1 5 10 15 Cys Gln Leu IleThr Ala Glu Thr Tyr Ser Arg Gly Glu Gln Lys His 20 25 30 His Ala Leu ArgSer Thr Asp Arg Asn Ser Lys Leu Thr Arg Thr Cys 35 40 45 Asn Thr Pro ThrGlu Tyr Cys Thr Leu His Arg His Cys Cys Ser Gly 50 55 60 Tyr Cys His LysThr Ile Gln Ala Cys Ser 65 70 18 28 PRT Conus arenatus PEPTIDE (1)..(28)Xaa at residue 7 is Glu or gamma-carboxy Glu; Xaa at residue 5 is Pro orHyp; Xaa at residue 8 and 19 is Tyr, 125I-Tyr, mono-iodo-Tyr,di-iodo-Tyr, O-sulpho-Tyr or O-phospho-Tyr 18 Thr Cys Asn Thr Xaa ThrXaa Xaa Cys Thr Leu His Arg His Cys Cys 1 5 10 15 Ser Gly Xaa Cys HisLys Thr Ile Gln Ala Cys Ser 20 25 19 332 DNA Conus arenatus 19accaaaacca tcatcaaaat gaaactgacg tgcgtgttga tcatcgccgt gctgttcctg 60acggcctgtc aactcattac agctgagact tactccagag gtgagcagat gcaccgtgct 120ctgaggtcaa ctgacaaaaa ctccaagttg actaggcagt gcacgcctaa cggtggatct 180tgttctcgtc attttcactg ctgcagcctc tattgcaata aaagtactgg cgtatgtatt 240gcaacctcat acccgtgagt ggtcatgaac cactcaatac cctctcctct ggaggcttca 300gaggaactgc attgaaataa aagccgcatt gc 332 20 79 PRT Conus arenatus 20 MetLys Leu Thr Cys Val Leu Ile Ile Ala Val Leu Phe Leu Thr Ala 1 5 10 15Cys Gln Leu Ile Thr Ala Glu Thr Tyr Ser Arg Gly Glu Gln Met His 20 25 30Arg Ala Leu Arg Ser Thr Asp Lys Asn Ser Lys Leu Thr Arg Gln Cys 35 40 45Thr Pro Asn Gly Gly Ser Cys Ser Arg His Phe His Cys Cys Ser Leu 50 55 60Tyr Cys Asn Lys Ser Thr Gly Val Cys Ile Ala Thr Ser Tyr Pro 65 70 75 2133 PRT Conus arenatus PEPTIDE (1)..(33) Xaa at residue 1 is Gln orpyro-Glu; Xaa at residue 4 and 33 is Pro or Hyp; Xaa at residue 19 and32 is Tyr, 125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr orO-phospho-Tyr 21 Xaa Cys Thr Xaa Asn Gly Gly Ser Cys Ser Arg His Phe HisCys Cys 1 5 10 15 Ser Leu Xaa Cys Asn Lys Ser Thr Gly Val Cys Ile AlaThr Ser Xaa 20 25 30 Xaa 22 332 DNA Conus arenatus 22 ggatccatgaaactgacgtg catggtgatt atcgccgtgc tgttcctgac ggcctgtcaa 60 ctcattacagctgagactta ctccagaggt gagcagaagc accatgctct gaggtcaact 120 gacaaaaactccaagttgac caggacatgc aacactccca ccgaatattg tactttgcat 180 caacactgctgcagcggcta ctgccataaa acaatccagg catgttcata ataccggtga 240 gtggtcatgaaccactcaat accctctcct ctggaggctt cagaggaact gcattgaaat 300 aaaaccgcattacaaaaaaa aaaaaaaaaa aa 332 23 74 PRT Conus arenatus 23 Met Lys Leu ThrCys Met Val Ile Ile Ala Val Leu Phe Leu Thr Ala 1 5 10 15 Cys Gln LeuIle Thr Ala Glu Thr Tyr Ser Arg Gly Glu Gln Lys His 20 25 30 His Ala LeuArg Ser Thr Asp Lys Asn Ser Lys Leu Thr Arg Thr Cys 35 40 45 Asn Thr ProThr Glu Tyr Cys Thr Leu His Gln His Cys Cys Ser Gly 50 55 60 Tyr Cys HisLys Thr Ile Gln Ala Cys Ser 65 70 24 28 PRT Conus arenatus PEPTIDE(1)..(28) Xaa at residue 7 is Glu or gamma-carboxy Glu; Xaa at residue 5is Pro or Hyp; Xaa at residue 8 and 19 is Tyr, 125I-Tyr, mono-iodo-Tyr,di-iodo-Tyr, O-sulpho-Tyr or O-phospho-Tyr 24 Thr Cys Asn Thr Xaa ThrXaa Xaa Cys Thr Leu His Gln His Cys Cys 1 5 10 15 Ser Gly Xaa Cys HisLys Thr Ile Gln Ala Cys Ser 20 25 25 394 DNA Conus arenatus 25ggatccatga aactgacgtg tatggtgatc atcgccgtac tgttcctgac ggcctgtcaa 60ctcattacag ctgagactta ctccagaggt aagcagatgc accgcgctct gaggtcaact 120gacaaaaact cccagttgac cagggaatgc acacctcccg gtggagcttg tggtttacct 180acacactgct gcgggttttg cgatactgca aacaacagat gtctgtaaag ctggtctggc 240gtctgatatt ccccttctgt gctctatcct ctttggcctg agtcatccgt acctgtgagt 300ggtcatgaac tactcaatac cctctcctct ggaggcttca gaggaactac aatgaaataa 360aacccgcatt gcagagaaaa aaaaaaaaaa aaaa 394 26 73 PRT Conus arenatus 26Met Lys Leu Thr Cys Met Val Ile Ile Ala Val Leu Phe Leu Thr Ala 1 5 1015 Cys Gln Leu Ile Thr Ala Glu Thr Tyr Ser Arg Gly Lys Gln Met His 20 2530 Arg Ala Leu Arg Ser Thr Asp Lys Asn Ser Gln Leu Thr Arg Glu Cys 35 4045 Thr Pro Pro Gly Gly Ala Cys Gly Leu Pro Thr His Cys Cys Gly Phe 50 5560 Cys Asp Thr Ala Asn Asn Arg Cys Leu 65 70 27 27 PRT Conus arenatusPEPTIDE (1)..(27) Xaa at residue 1 is Glu or gamma-carboxy Glu; Xaa atresidue 4, 5 and 12 is Pro or Hyp 27 Xaa Cys Thr Xaa Xaa Gly Gly Ala CysGly Leu Xaa Thr His Cys Cys 1 5 10 15 Gly Phe Cys Asp Thr Ala Asn AsnArg Cys Leu 20 25 28 345 DNA Conus arenatus misc_feature (1)..(345) nmay be any nucldeotide 28 ggatccatga aactgacgtg cgtggtgatt atcgccgtgctgttcctgac ggcctgtcaa 60 ctcattacag ctgagactta ctccagaggt gagcagaatcaccatgttct gaggtcaact 120 gacaaaaact ccaagttgac caggacatgc aacactcccactgaatattg tactttgcat 180 caacactgct gcagcggcca ctgccataaa acaatccaggcatgtgcata ataccggtgg 240 gtggtcatga accactcaat accctctcct ctggaggcttcagaggaact gcattgaaat 300 aaaaccgcat tgcaatgaan aaaaaaaaaa aaaaaaaaaaaaaaa 345 29 74 PRT Conus arenatus 29 Met Lys Leu Thr Cys Val Val IleIle Ala Val Leu Phe Leu Thr Ala 1 5 10 15 Cys Gln Leu Ile Thr Ala GluThr Tyr Ser Arg Gly Glu Gln Asn His 20 25 30 His Val Leu Arg Ser Thr AspLys Asn Ser Lys Leu Thr Arg Thr Cys 35 40 45 Asn Thr Pro Thr Glu Tyr CysThr Leu His Gln His Cys Cys Ser Gly 50 55 60 His Cys His Lys Thr Ile GlnAla Cys Ala 65 70 30 28 PRT Conus arenatus PEPTIDE (1)..(28) Xaa atresidue 7 is Glu or gamma-carboxy Glu; Xaa at residue 5 is Pro or Hyp;Xaa at residue8 is Tyr, 125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr,O-sulpho-Tyr or O-phospho-Tyr 30 Thr Cys Asn Thr Xaa Thr Xaa Xaa Cys ThrLeu His Gln His Cys Cys 1 5 10 15 Ser Gly His Cys His Lys Thr Ile GlnAla Cys Ala 20 25 31 322 DNA Conus arenatus 31 ggatccatga aactgacgtgtgtggtgatc atcgccgtgc tgttcctgac ggcctgtcaa 60 ctcactacag gtgagcagaaggaccatgct ctgaggtcaa ctgacaaaaa ctccaagttg 120 actaggcagt gctcgcctatcggtggatat tgtactcttc atattcactg ctgcagcaac 180 cattgcatta aacctatcggccgatgtgtg gcaacctgat acccgtgcgt ggtcatgaac 240 ccctcaatac cctctcctctggaggcttca gaggaactgc attgaaataa aaccgcattg 300 caataaaaaa aaaaaaaaaa aa322 32 70 PRT Conus arenatus 32 Met Lys Leu Thr Cys Val Val Ile Ile AlaVal Leu Phe Leu Thr Ala 1 5 10 15 Cys Gln Leu Thr Thr Gly Glu Gln LysAsp His Ala Leu Arg Ser Thr 20 25 30 Asp Lys Asn Ser Lys Leu Thr Arg GlnCys Ser Pro Ile Gly Gly Tyr 35 40 45 Cys Thr Leu His Ile His Cys Cys SerAsn His Cys Ile Lys Pro Ile 50 55 60 Gly Arg Cys Val Ala Thr 65 70 33 30PRT Conus arenatus PEPTIDE (1)..(30) Xaa at residue 1 is Gln orpyro-Glu; Xaa at residue 4 and 23 is Pro or Hyp; Xaa at residue 8 isTyr, 125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr or O-phospho-Tyr33 Xaa Cys Ser Xaa Ile Gly Gly Xaa Cys Thr Leu His Ile His Cys Cys 1 510 15 Ser Asn His Cys Ile Lys Xaa Ile Gly Arg Cys Val Ala Thr 20 25 3034 318 DNA Conus arenatus 34 ggatccatga aactgacgtg cgtggtgatc atcgccgtgctgttcctgac ggcctgtcaa 60 ctcactacag gtgagcagaa ggaccatgct ctgaggtcaactgacaaaaa ctccaagttg 120 actaggcagt gcttgcctaa cggtggatat tgtactcttcatattcactg ctgcagcgac 180 cattgcatta aacctatcga ccgatgtgtg gcaacctgatacccgggcgt ggtcatgaac 240 ccctcaatac cctctcctct ggaggcttca gaggaactgcattgaaataa aaccgcatta 300 caaaaaaaaa aaaaaaaa 318 35 70 PRT Conusarenatus 35 Met Lys Leu Thr Cys Val Val Ile Ile Ala Val Leu Phe Leu ThrAla 1 5 10 15 Cys Gln Leu Thr Thr Gly Glu Gln Lys Asp His Ala Leu ArgSer Thr 20 25 30 Asp Lys Asn Ser Lys Leu Thr Arg Gln Cys Leu Pro Asn GlyGly Tyr 35 40 45 Cys Thr Leu His Ile His Cys Cys Ser Asp His Cys Ile LysPro Ile 50 55 60 Asp Arg Cys Val Ala Thr 65 70 36 30 PRT Conus arenatusPEPTIDE (1)..(30) Xaa at residue 1 is Gln or pyro-Glu; Xaa at residue 4and 23 is Pro or Hyp; Xaa at residue 8 is Tyr, 125I-Tyr, mono-iodo-Tyr,di-iodo-Tyr, O-sulpho-Tyr or O-phospho-Tyr 36 Xaa Cys Leu Xaa Asn GlyGly Xaa Cys Thr Leu His Ile His Cys Cys 1 5 10 15 Ser Asp His Cys IleLys Xaa Ile Asp Arg Cys Val Ala Thr 20 25 30 37 374 DNA Conus aurisiacus37 atgaaactga cgtgtgtggt gatcgtcgcc gtgctgctcc tgacggcctg tcaactcatc 60acagctgatg actccagagg tacgcagaag catcgttccc tgagctcggc caccaaactc 120tccatgtcga ctcgctgcaa gggtaaagga aaaccatgca gtaggatttc gtataactgc 180tgcaccggtt cttgcagatc aggtaaatgt ggctgatcca gcgcctgatc ttcccccttc 240tgtgctctat ccttttctgc ctgagtcctc cttacctgag agtggtcatg aaccactcat 300cacctgctcc tctggaggcc ccagaggagc tacattgaaa taaaagtcgc attgcaaaaa 360aaaaaaaaaa aaaa 374 38 71 PRT Conus aurisiacus 38 Met Lys Leu Thr CysVal Val Ile Val Ala Val Leu Leu Leu Thr Ala 1 5 10 15 Cys Gln Leu IleThr Ala Asp Asp Ser Arg Gly Thr Gln Lys His Arg 20 25 30 Ser Leu Ser SerAla Thr Lys Leu Ser Met Ser Thr Arg Cys Lys Gly 35 40 45 Lys Gly Lys ProCys Ser Arg Ile Ser Tyr Asn Cys Cys Thr Gly Ser 50 55 60 Cys Arg Ser GlyLys Cys Gly 65 70 39 25 PRT Conus aurisiacus PEPTIDE (1)..(25) Xaa atresidue 7 is Pro or Hyp; Xaa at residue 13 is Tyr, 125I-Tyr,mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr or O-phospho-Tyr 39 Cys Lys GlyLys Gly Lys Xaa Cys Ser Arg Ile Ser Xaa Asn Cys Cys 1 5 10 15 Thr GlySer Cys Arg Ser Gly Lys Cys 20 25 40 380 DNA Conus aurisiacus 40atgaaactga cgtgtgtggt gatcgtcgcc gtgctgctcc tgacggcctg tcaactcatc 60acagctgatg actccagagg tacgcagaag catcgttccc tgaggtcgaa gaccaaactc 120tccatgtcga ctggctgcat ggaagccgga tcttattgcg gctctactac gagaatctgc 180tgcggttttt gcgcttattt cggcaaaaaa tgtattgact atcccagcaa ctgatcttcc 240ccctactgtg ctctatcctt ttctgcctga gtcctcctta cctgagagtg gtcatgaacc 300actcatcacc tgctcctctg gaggccccag aggagctaca ttgaaataaa atcgcattgc 360taaaaaaaaa aaaaaaaaaa 380 41 77 PRT Conus aurisiacus 41 Met Lys Leu ThrCys Val Val Ile Val Ala Val Leu Leu Leu Thr Ala 1 5 10 15 Cys Gln LeuIle Thr Ala Asp Asp Ser Arg Gly Thr Gln Lys His Arg 20 25 30 Ser Leu ArgSer Lys Thr Lys Leu Ser Met Ser Thr Gly Cys Met Glu 35 40 45 Ala Gly SerTyr Cys Gly Ser Thr Thr Arg Ile Cys Cys Gly Phe Cys 50 55 60 Ala Tyr PheGly Lys Lys Cys Ile Asp Tyr Pro Ser Asn 65 70 75 42 32 PRT Conusaurisiacus PEPTIDE (1)..(32) Xaa at residue 3 is Glu or gamma-carboxyGlu; Xaa at residue 30 is Pro or Hyp; Xaa at residue 7, 21 and 29 isTyr, 125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr or O-phospho-Tyr42 Cys Met Xaa Ala Gly Ser Xaa Cys Gly Ser Thr Thr Arg Ile Cys Cys 1 510 15 Gly Phe Cys Ala Xaa Phe Gly Lys Lys Cys Ile Asp Xaa Xaa Ser Asn 2025 30 43 373 DNA Conus aurisiacus 43 accaaaacca tcatcaaaat gaaactgacgtgtgtggtga tcgtcgccgt gctgctcctg 60 acggcctgtc aactcatcac agctgatgactccagaggta cgcagaagca tcgttccctg 120 agctcggcca ccaaactctc catgtcgactcgctgcaagg ctaaaggaaa accatgcagt 180 aggattgcgt ataactgctg caccggttcttgcagatcag gtaaatgtgg ctgatccagt 240 gcctgatctt cccccttctg tgctctatccttttctgcct gagtcctcct tacctgagag 300 tggtcatgaa ccactcatca cctgctcctctggaggcccc agaggagcta cattgaaata 360 aaagccgcat tgc 373 44 71 PRT Conusaurisiacus 44 Met Lys Leu Thr Cys Val Val Ile Val Ala Val Leu Leu LeuThr Ala 1 5 10 15 Cys Gln Leu Ile Thr Ala Asp Asp Ser Arg Gly Thr GlnLys His Arg 20 25 30 Ser Leu Ser Ser Ala Thr Lys Leu Ser Met Ser Thr ArgCys Lys Ala 35 40 45 Lys Gly Lys Pro Cys Ser Arg Ile Ala Tyr Asn Cys CysThr Gly Ser 50 55 60 Cys Arg Ser Gly Lys Cys Gly 65 70 45 25 PRT Conusaurisiacus PEPTIDE (1)..(25) Xaa at residue 7 is Pro or Hyp; Xaa atresidue 13 is Tyr, 125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr orO-phospho-Ty 45 Cys Lys Ala Lys Gly Lys Xaa Cys Ser Arg Ile Ala Xaa AsnCys Cys 1 5 10 15 Thr Gly Ser Cys Arg Ser Gly Lys Cys 20 25 46 379 DNAConus aurisiacus 46 accaaaacca tcatcaaaat gaaactgacg tgtgtggtgatcgtcgccgt gctgctcctg 60 acgacctgtc aactcatcac agctgatgac tccagaggtacgcaggagca tcgtgccctg 120 aggtcgaaga caaaactctc catgttaact ttgcgctgcgcatcttacgg aaaaccttgt 180 ggtattgaca acgactgctg caatgcatgc gatccaggaagaaatatatg tacgtagctg 240 atccagcgcc tgatcttccc ccttctgtgc tctatccttttctgcccgag tcctccttac 300 ctgagagtgg tcatgaacca ctcatcacct gctccctggaggcctcagag gagctacaat 360 gaaataaaag ccgcattgc 379 47 72 PRT Conusaurisiacus 47 Met Lys Leu Thr Cys Val Val Ile Val Ala Val Leu Leu LeuThr Thr 1 5 10 15 Cys Gln Leu Ile Thr Ala Asp Asp Ser Arg Gly Thr GlnGlu His Arg 20 25 30 Ala Leu Arg Ser Lys Thr Lys Leu Ser Met Leu Thr LeuArg Cys Ala 35 40 45 Ser Tyr Gly Lys Pro Cys Gly Ile Asp Asn Asp Cys CysAsn Ala Cys 50 55 60 Asp Pro Gly Arg Asn Ile Cys Thr 65 70 48 26 PRTConus aurisiacus PEPTIDE (1)..(26) Xaa at residue 7 and 20 is Pro orHyp; Xaa at residue 4 is Tyr, 125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr,O-sulpho-Tyr or O-phospho-Tyr 48 Cys Ala Ser Xaa Gly Lys Xaa Cys Gly IleAsp Asn Asp Cys Cys Asn 1 5 10 15 Ala Cys Asp Xaa Gly Arg Asn Ile CysThr 20 25 49 382 DNA Conus bullatus 49 accaaaacca tcatcaaaat gaaactgacgtgtgtggcga tcgtcgccgt gctgctcctg 60 acggcctgtc agctcattac agctgaagactccagaggta cgcatgagca tcttgccctg 120 aagtcgacct ccaaagtctc caagtcgactagctgcatgg aagccggatc ttattgcgga 180 cctgctacta cgaaaatctg ctgcgatttttgcagtccat tcagcgatag atgtatgaac 240 aatcccaaca attgatcttc ccccttgtgtgctccatcct tttctgcctg agtcctcctt 300 acctgagagt ggtcatgaac cactcatcacctactcctct ggaggcttca gaggagctac 360 attgaaataa aagccgcatt gc 382 50 78PRT Conus bullatus 50 Met Lys Leu Thr Cys Val Ala Ile Val Ala Val LeuLeu Leu Thr Ala 1 5 10 15 Cys Gln Leu Ile Thr Ala Glu Asp Ser Arg GlyThr His Glu His Leu 20 25 30 Ala Leu Lys Ser Thr Ser Lys Val Ser Lys SerThr Ser Cys Met Glu 35 40 45 Ala Gly Ser Tyr Cys Gly Pro Ala Thr Thr LysIle Cys Cys Asp Phe 50 55 60 Cys Ser Pro Phe Ser Asp Arg Cys Met Asn AsnPro Asn Asn 65 70 75 51 36 PRT Conus bullatus PEPTIDE (1)..(36) Xaa atresidue 6 is Glu or gamma-carboxy Glu; Xaa at residue 13,25 and 34 isPro or Hyp; Xaa at residue10 is Tyr, 125I-Tyr, mono-iodo-Tyr,di-iodo-Tyr, O-sulpho-Tyr or O-phospho-Tyr 51 Ser Thr Ser Cys Met XaaAla Gly Ser Xaa Cys Gly Xaa Ala Thr Thr 1 5 10 15 Lys Ile Cys Cys AspPhe Cys Ser Xaa Phe Ser Asp Arg Cys Met Asn 20 25 30 Asn Xaa Asn Asn 3552 400 DNA Conus bullatus 52 accaaaacca tcatcaaaat gaaactgacg tgtgtggtgatcgtcgccgt gctgctcctg 60 acggcctgtc agctcattac agctgaagac tccagaggtacgcagttgca tcgtgccctg 120 aggaaggcca ccaaacaccc tgtgtcgact cgctgcattactccaggaac acgatgtaag 180 gttccgagcc aatgctgcag aggtccttgc aagaacggtcgttgtactcc atccccttct 240 gaatggtaaa tgtggttgat ccagcgcctg atcttcccccttcgtcgtgc tccatccttt 300 tctgcctgag tcctccttac ctgagagtgg tcatgaaccactcatcacct actcccctgg 360 aggcttcaga ggagctacat tgaaataaaa gccgcattgc400 53 76 PRT Conus bullatus 53 Met Lys Leu Thr Cys Val Val Ile Val AlaVal Leu Leu Leu Thr Ala 1 5 10 15 Cys Gln Leu Ile Thr Ala Glu Asp SerArg Gly Thr Gln Leu His Arg 20 25 30 Ala Leu Arg Lys Ala Thr Lys His ProVal Ser Thr Arg Cys Ile Thr 35 40 45 Pro Gly Thr Arg Cys Lys Val Pro SerGln Cys Cys Arg Gly Pro Cys 50 55 60 Lys Asn Gly Arg Cys Thr Pro Ser ProSer Glu Trp 65 70 75 54 31 PRT Conus bullatus PEPTIDE (1)..(31) Xaa atresidue 30 is Glu or gamma-carboxy Glu; Xaa at residue 4, 11, 18, 26 and28 is Pro or Hyp; Xaa at residue 31is Trp or Bromo Trp 54 Cys Ile ThrXaa Gly Thr Ala Cys Lys Val Xaa Ser Gln Cys Cys Arg 1 5 10 15 Gly XaaCys Lys Asn Gly Arg Cys Thr Xaa Ser Xaa Ser Xaa Xaa 20 25 30 55 379 DNAConus bullatus 55 accaaaacca tcatcaaaat gaaactgacg tgtgtggcga tcgtcgccgtgctgctcctg 60 acggcctgtc agctcattac agctgaggac tccagagata cgcagaagcatcgtgccctg 120 aggtcggaca ccaaactctc catgttgact ttgcgctgcg caacttacggaaaaccttgt 180 ggtattcaaa acgactgctg caatacatgc gatccagcca gaaggacatgtacgtagctg 240 atccggcgtc ttgatcctcc gcttctgtgc tccatctttt ctgcctgagtcctccttacc 300 tgagagtggt catgaaccac tcatcaccta ctcctctgga ggctttagaggagctacatt 360 gaaataaaag ccgcattgc 379 56 72 PRT Conus bullatus 56 MetLys Leu Thr Cys Val Ala Ile Val Ala Val Leu Leu Leu Thr Ala 1 5 10 15Cys Gln Leu Ile Thr Ala Glu Asp Ser Arg Asp Thr Gln Lys His Arg 20 25 30Ala Leu Arg Ser Asp Thr Lys Leu Ser Met Leu Thr Leu Arg Cys Ala 35 40 45Thr Tyr Gly Lys Pro Cys Gly Ile Gln Asn Asp Cys Cys Asn Thr Cys 50 55 60Asp Pro Ala Arg Arg Thr Cys Thr 65 70 57 26 PRT Conus bullatus PEPTIDE(1)..(26) Xaa at residue 7 and 20 is Pro or Hyp; Xaa at residue 4 isTyr, 125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr or O-phospho-Tyr57 Cys Ala Thr Xaa Gly Lys Xaa Cys Gly Ile Gln Asn Asp Cys Cys Asn 1 510 15 Thr Cys Asp Xaa Ala Arg Arg Thr Cys Thr 20 25 58 373 DNA Conusbullatus 58 accaaaacca tcatcaaaat gaaactgacg tgtgtggcga tcgtcgccgtgctgctcctg 60 acggcctgtc agctcattac agctgaagac tccagaggta cgcagttgcatcgtgccctg 120 aggaagacca ccaaactctc cttgtcgact cgctgcaagg gtccaggagcatcatgtata 180 aggattgcgt ataactgctg caagtattct tgcagaaatg gtaaatgtggctgatccagc 240 gcctgatctt cccccttgtg tgctccatcc ttttctgcct gagtcctccttacctgagag 300 tggtcatgaa ccactcatca cctactcctc tggaggcttc agaggagctacattgaaata 360 aaagccgcat tgc 373 59 71 PRT Conus bullatus 59 Met LysLeu Thr Cys Val Ala Ile Val Ala Val Leu Leu Leu Thr Ala 1 5 10 15 CysGln Leu Ile Thr Ala Glu Asp Ser Arg Gly Thr Gln Leu His Arg 20 25 30 AlaLeu Arg Lys Thr Thr Lys Leu Ser Leu Ser Thr Arg Cys Lys Gly 35 40 45 ProGly Ala Ser Cys Ile Arg Ile Ala Tyr Asn Cys Cys Lys Tyr Ser 50 55 60 CysArg Asn Gly Lys Cys Gly 65 70 60 25 PRT Conus bullatus PEPTIDE (1)..(25)Xaa at residue 4 is Pro or Hyp; Xaa at residue 13 and 18 is Tyr,125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr or O-phospho-Tyr 60Cys Lys Gly Xaa Gly Ala Ser Cys Ile Arg Ile Ala Xaa Asn Cys Cys 1 5 1015 Lys Xaa Ser Cys Arg Asn Gly Lys Cys 20 25 61 382 DNA Conus bullatus61 atcaaaacca tcatcaaaat gaaactgacg tgtgtggtga tcgtcgccgt gctgctcctg 60acggcctgtc agctcattac agctgaagac tccagaggta cgcatgagca tcttgccctg 120aagtcgacct ccaaagtctc caagtcgact agctgcatgg cagccggatc ttattgcgga 180cctgctacta cgaatatctg ctgcgatttt tgcagtccat tcagcgatag atgtatgaaa 240aagcccaaca attgatcttc ccccttctgt gctctatcct tttctgcctg agtcctcctt 300acctgagagt ggtcatgaac cactcatcac ctactcctct ggaggcttca gaggagctac 360attgaaataa aagccgcatt gc 382 62 78 PRT Conus bullatus 62 Met Lys Leu ThrCys Val Val Ile Val Ala Val Leu Leu Leu Thr Ala 1 5 10 15 Cys Gln LeuIle Thr Ala Glu Asp Ser Arg Gly Thr His Glu His Leu 20 25 30 Ala Leu LysSer Thr Ser Lys Val Ser Lys Ser Thr Ser Cys Met Ala 35 40 45 Ala Gly SerTyr Cys Gly Pro Ala Thr Thr Asn Ile Cys Cys Asp Phe 50 55 60 Cys Ser ProPhe Ser Asp Arg Cys Met Lys Lys Pro Asn Asn 65 70 75 63 36 PRT Conusbullatus PEPTIDE (1)..(36) Xaa at residue 13, 25 and 34 is Pro or Hyp;Xaa at residue 10 is Tyr, 125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr,O-sulpho-Tyr or O-phospho-Tyr 63 Ser Thr Ser Cys Met Ala Ala Gly Ser XaaCys Gly Xaa Ala Thr Thr 1 5 10 15 Asn Ile Cys Cys Asp Phe Cys Ser XaaPhe Ser Asp Arg Cys Met Lys 20 25 30 Lys Xaa Asn Asn 35 64 373 DNA Conusbullatus 64 accaaaacca tcatcaaaat gaaactgacg tgtgtggtga tcgtcgccgtgctgctcctg 60 acggcctgtc agctcattat agctgaggac tccagaggta cgcagttgcatcgtgccctg 120 aggaaggcca ccaaactctc cgtgtcgact cgctgcaaga gtaaaggatcatcatgtcat 180 aggacttcgt atgactgctg cacgggttct tgcagaaatg gtagatgtggctgatccagc 240 gcctgatctt cccccttctg tgctccatcc ttttctgcct gagtcctccttacctgagag 300 tggtcatgaa ccactcatca cctactcctc tggaggcttc agaggagctacattgaaata 360 aaagccgcat tgc 373 65 71 PRT Conus bullatus 65 Met LysLeu Thr Cys Val Val Ile Val Ala Val Leu Leu Leu Thr Ala 1 5 10 15 CysGln Leu Ile Ile Ala Glu Asp Ser Arg Gly Thr Gln Leu His Arg 20 25 30 AlaLeu Arg Lys Ala Thr Lys Leu Ser Val Ser Thr Arg Cys Lys Ser 35 40 45 LysGly Ser Ser Cys His Arg Thr Ser Tyr Asp Cys Cys Thr Gly Ser 50 55 60 CysArg Asn Gly Arg Cys Gly 65 70 66 25 PRT Conus bullatus PEPTIDE (1)..(25)Xaa at residue 13 is Tyr, 125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr,O-sulpho-Tyr or O-phospho-Tyr 66 Cys Lys Ser Lys Gly Ser Ser Cys His ArgThr Ser Xaa Asp Cys Cys 1 5 10 15 Thr Gly Ser Cys Arg Asn Gly Arg Cys 2025 67 321 DNA Conus caracteristicus 67 ggatccatga aactgacgtg cgtggtgatcatcgccgtgc tgttcctgac ggcctgtcaa 60 ctcattacag gtgagcagaa ggaccatgctctgaggtcaa ctgacaaaaa ctccaagttg 120 actaggcagt gctcggctaa cggtggatcttgtactcgtc attttcactg ctgcagcctc 180 tattgcaata aagattccag tgtatgtgtggcaacctcat acccgtgagt ggccatgaac 240 ccctcaatac cctctcctct ggaggcttcagaggaactgc attgaaataa aaccgcatta 300 caaaaaaaaa aaaaaaaaaa a 321 68 73PRT Conus caracteristicus 68 Met Lys Leu Thr Cys Val Val Ile Ile Ala ValLeu Phe Leu Thr Ala 1 5 10 15 Cys Gln Leu Ile Thr Gly Glu Gln Lys AspHis Ala Leu Arg Ser Thr 20 25 30 Asp Lys Asn Ser Lys Leu Thr Arg Gln CysSer Ala Asn Gly Gly Ser 35 40 45 Cys Thr Arg His Phe His Cys Cys Ser LeuTyr Cys Asn Lys Asp Ser 50 55 60 Ser Val Cys Val Ala Thr Ser Tyr Pro 6570 69 33 PRT Conus caracteristicus PEPTIDE (1)..(33) Xaa at residue 1 isGln or pyro-Glu; Xaa at residue 33 is Pro or Hyp; Xaa at residue 19 and32 is Tyr, 125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr orO-phospho- Tyr 69 Xaa Cys Ser Ala Asn Gly Gly Ser Cys Thr Arg His PheHis Cys Cys 1 5 10 15 Ser Leu Xaa Cys Asn Lys Asp Ser Ser Val Cys ValAla Thr Ser Xaa 20 25 30 Xaa 70 26 PRT Conus catus 70 Cys Lys Ser ThrGly Ala Ser Cys Arg Arg Thr Ser Tyr Asp Cys Cys 1 5 10 15 Thr Gly SerCys Arg Ser Gly Arg Cys Gly 20 25 71 25 PRT Conus catus PEPTIDE(1)..(25) Xaa at residue 13 is Tyr, 125I-Tyr, mono-iodo- Tyr,di-iodo-Tyr, O-sulpho-Tyr or O-phospho-Tyr 71 Cys Lys Ser Thr Gly AlaSer Cys Arg Arg Thr Ser Xaa Asp Cys Cys 1 5 10 15 Thr Gly Ser Cys ArgSer Gly Arg Cys 20 25 72 229 DNA Conus catus 72 tcgactcgct gccagggtagaggagcatca tgtcgtaaga ctatgtataa ctgctgcagc 60 ggttcttgca acagaggtagttgtggctga tccggcgcct gatcttcccc cttccgtgct 120 ctatcctttt ctgcctgattcctccttacc tgagagcggt catgaaccac tcatcacctg 180 ctcctctgga ggcctcagaggagctacatt gaaataaaag ccgcattgc 229 73 29 PRT Conus catus 73 Ser Thr ArgCys Gln Gly Arg Gly Ala Ser Cys Arg Lys Thr Met Tyr 1 5 10 15 Asn CysCys Ser Gly Ser Cys Asn Arg Gly Ser Cys Gly 20 25 74 25 PRT Conus catusPEPTIDE (1)..(25) Xaa at residue 13 is Tyr, 125I-Tyr, mono-iodo- Tyr,di-iodo-Tyr, O-sulpho-Tyr or O-phospho-Tyr 74 Cys Gln Gly Arg Gly AlaSer Cys Arg Lys Thr Met Xaa Asn Cys Cys 1 5 10 15 Ser Gly Ser Cys AsnArg Gly Ser Cys 20 25 75 235 DNA Conus catus 75 tcgacacgct gcttgcctgccggagagtct tgccttttta gtaggattag atgctgcggt 60 acttgcagtt cagtcttaaagtcatgtgtg agctgatcca gctgctgatc ttcctcctcc 120 tgtgctccat ccttttctgcctgagtcctc cttatctgag agtggtcatg aaccactcac 180 cacctactct tctggaggcttcagaggagc tacagtgaaa taaaagccgc attgc 235 76 31 PRT Conus catus 76 SerThr Arg Cys Leu Pro Ala Gly Glu Ser Cys Leu Phe Ser Arg Ile 1 5 10 15Arg Cys Cys Gly Thr Cys Ser Ser Val Leu Lys Ser Cys Val Ser 20 25 30 7728 PRT Conus catus PEPTIDE (1)..(28) Xaa at residue 6 is Glu orgamma-carboxy Glu; Xaa at residue 3 is Pro or Hyp 77 Cys Leu Xaa Ala GlyXaa Ser Cys Leu Phe Ser Arg Ile Arg Cys Cys 1 5 10 15 Gly Thr Cys SerSer Val Leu Lys Ser Cys Val Ser 20 25 78 227 DNA Conus catus 78tcgacacgct gccagggtag aggaggacca tgtactaagg ctgtgtttaa ctgctgcagc 60ggttcttgca acagaggtag atgtggctga tccagcgcct gatcttcccc cttctgtgct 120ctatcctttt ctgcctgagt cctccttact gagagtagtc atgaaccact catcacctac 180tcctctggag gcctcagaga gctacattga aataaaagcc gcattgc 227 79 29 PRT Conuscatus 79 Ser Thr Arg Cys Gln Gly Arg Gly Gly Pro Cys Thr Lys Ala Val Phe1 5 10 15 Asn Cys Cys Ser Gly Ser Cys Asn Arg Gly Arg Cys Gly 20 25 8025 PRT Conus catus PEPTIDE (1)..(25) Xaa at residue 7 is Pro or Hyp 80Cys Gln Gly Arg Gly Gly Xaa Cys Thr Lys Ala Val Phe Asn Cys Cys 1 5 1015 Ser Gly Ser Cys Asn Arg Gly Arg Cys 20 25 81 236 DNA Conus catus 81ttaactttgc gctgcgcaac ttacggaaaa ccttgtggta ttcaaaacga ctgctgcaat 60acatgcgatc cagccagaaa gacatgtacg tagctgatcc ggcgtctgat ctcccccctt 120ctgtgctcta tccttttctg cctgagtcct ccttacctga gagtggtcat gaaccactca 180tcacctgctc ctctggaggc ctcgggggag ctacattgaa ataaaagccg cattgc 236 82 30PRT Conus catus 82 Leu Thr Leu Arg Cys Ala Thr Tyr Gly Lys Pro Cys GlyIle Gln Asn 1 5 10 15 Asp Cys Cys Asn Thr Cys Asp Pro Ala Arg Lys ThrCys Thr 20 25 30 83 26 PRT Conus catus PEPTIDE (1)..(26) Xaa at residue7 and 20 is Pro or Hyp; Xaa at residue 4 is Tyr, 125I-Tyr,mono-iodo-Tyr, di-iodo- Tyr, O-sulpho-Tyr or O-phospho-Tyr 83 Cys AlaThr Xaa Gly Lys Xaa Cys Gly Ile Gln Asn Asp Cys Cys Asn 1 5 10 15 ThrCys Asp Xaa Ala Arg Lys Thr Cys Thr 20 25 84 229 DNA Conus catus 84tcgactcgct gccggggtag aggaggacca tgtactaagg ctatgtttaa ctgctgcagc 60ggttcttgca acagaggtag atgtggctga tccagcgcct gatcttcccc cttctgtgct 120ctatcctttt ctgcctgagt cctccttaac tgagagtagt catgaaccac tcatcaccta 180ctcctctgga ggcctcagag aagcatcatt gaaataaaag ccgcattgc 229 85 29 PRTConus catus 85 Ser Thr Arg Cys Arg Gly Arg Gly Gly Pro Cys Thr Lys AlaMet Phe 1 5 10 15 Asn Cys Cys Ser Gly Ser Cys Asn Arg Gly Arg Cys Gly 2025 86 25 PRT Conus catus PEPTIDE (1)..(25) Xaa at residue 7 is Pro orHyp 86 Cys Arg Gly Arg Gly Gly Xaa Cys Thr Lys Ala Met Phe Asn Cys Cys 15 10 15 Ser Gly Ser Cys Asn Arg Gly Arg Cys 20 25 87 374 DNA Conuscircumcisus 87 accaaaacca tcatcaaaat gaaactgacg tgtgtggtga tcgtcgccgtgctgctcctg 60 acgacctgtc aactcatcac agctgatgac tccagaggta cgcaggagcatcgtgccctg 120 aggtcggaca ccaaactccc catgtcgact cgctgcaagg gtaaaggagcatcatgtcgt 180 aagactatgt ataactgctg cagcggttct tgcagcaacg gtagatgtggctgatccagc 240 gcctgatctt cccccttctg ctgctctatc cttttctgcc tgagtcctccttacctgaga 300 gctggtcatg aaccactcat cacctgctcc tctggaggcc cagaggagctacattgaaat 360 aaaagccgca ttgc 374 88 71 PRT Conus circumcisus 88 MetLys Leu Thr Cys Val Val Ile Val Ala Val Leu Leu Leu Thr Thr 1 5 10 15Cys Gln Leu Ile Thr Ala Asp Asp Ser Arg Gly Thr Gln Glu His Arg 20 25 30Ala Leu Arg Ser Asp Thr Lys Leu Pro Met Ser Thr Arg Cys Lys Gly 35 40 45Lys Gly Ala Ser Cys Arg Lys Thr Met Tyr Asn Cys Cys Ser Gly Ser 50 55 60Cys Ser Asn Gly Arg Cys Gly 65 70 89 25 PRT Conus circumcisus PEPTIDE(1)..(25) Xaa at residue 13 is Tyr, 125I-Tyr, mono-iodo- Tyr,di-iodo-Tyr, O-sulpho-Tyr or O-phospho-Tyr 89 Cys Lys Gly Lys Gly AlaSer Cys Arg Lys Thr Met Xaa Asn Cys Cys 1 5 10 15 Ser Gly Ser Cys SerAsn Gly Arg Cys 20 25 90 379 DNA Conus circumcisus 90 accaaaaccatcatcaaaat gaaactgacg tgtgtggtga tcgtcgccgt gctgctcctg 60 acgacctgtcaactcatcac agctgatgac tccagaggta cgcagaagca tcgtgccctg 120 aggtcggccaccaaagtctc caagtcgact agctgcatgg aagccggatc ttattgccgc 180 tctactacgagaacctgctg cggttattgc tcttatttca gcaaaaaatg tattgacttt 240 cccagcaactgatcttcccc ctactgtgct ctatcctttt ctgcctgagt cctccttacc 300 tgagagtggtcatgaaccac tcatcaccct actcctctgg aggcccagag gagctacatt 360 gaaataaaagccgcattgc 379 91 77 PRT Conus circumcisus 91 Met Lys Leu Thr Cys Val ValIle Val Ala Val Leu Leu Leu Thr Thr 1 5 10 15 Cys Gln Leu Ile Thr AlaAsp Asp Ser Arg Gly Thr Gln Lys His Arg 20 25 30 Ala Leu Arg Ser Ala ThrLys Val Ser Lys Ser Thr Ser Cys Met Glu 35 40 45 Ala Gly Ser Tyr Cys ArgSer Thr Thr Arg Thr Cys Cys Gly Tyr Cys 50 55 60 Ser Tyr Phe Ser Lys LysCys Ile Asp Phe Pro Ser Asn 65 70 75 92 35 PRT Conus circumcisus PEPTIDE(1)..(35) Xaa at residue 6 is Glu or gamma-carboxy Glu; Xaa at residue33 is Pro or Hyp; Xaa at residue 10, 21 and 24 is Tyr, 125I-Tyr,mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr or O-phospho-Tyr 92 Ser Thr SerCys Met Xaa Ala Gly Ser Xaa Cys Arg Ser Thr Thr Arg 1 5 10 15 Thr CysCys Gly Xaa Cys Ser Xaa Phe Ser Lys Lys Cys Ile Asp Phe 20 25 30 Xaa SerAsn 35 93 379 DNA Conus circumcisus 93 accaaaacca tcatcaaaat gaaactgacgtgtgtggtga tcgtcgccgt gctgctcctg 60 acgacctgtc aactcatcac agctgatgactccagaggta cgcaggagca tcgtgccctg 120 aggtcggaca ccaaactccc catgtcgactcgctgcaaga gtaaaggagc aaaatgttca 180 aggcttatgt atgactgctg cagcggttcttgcagcaggt actcaggtag atgtggctga 240 tccagcgcct gatcttcccc cttctgctgctctatccttt tctgcctgag tcctccttac 300 ctgagagtgg tcatgaacca ctcatcacctactcctctgg aggcccagag gagctacatt 360 gaaataaaag ccgcattgc 379 94 73 PRTConus circumcisus 94 Met Lys Leu Thr Cys Val Val Ile Val Ala Val Leu LeuLeu Thr Thr 1 5 10 15 Cys Gln Leu Ile Thr Ala Asp Asp Ser Arg Gly ThrGln Glu His Arg 20 25 30 Ala Leu Arg Ser Asp Thr Lys Leu Pro Met Ser ThrArg Cys Lys Ser 35 40 45 Lys Gly Ala Lys Cys Ser Arg Leu Met Tyr Asp CysCys Ser Gly Ser 50 55 60 Cys Ser Arg Tyr Ser Gly Arg Cys Gly 65 70 95 27PRT Conus circumcisus PEPTIDE (1)..(27) Xaa at residue 13 and 23 is Tyr,125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr or O-phospho-Tyr 95Cys Lys Ser Lys Gly Ala Lys Cys Ser Arg Leu Met Xaa Asp Cys Cys 1 5 1015 Ser Gly Ser Cys Ser Arg Xaa Ser Gly Arg Cys 20 25 96 379 DNA Conuscircumcisus 96 accaaaacca tcatcaaaat gaaactgacg tgtgtggtga tcgtcgccgtgctgctcctg 60 acgacctgtc aactcatcac agctgatgac tccagaggta cgcagaagcatcgttccctg 120 acgtcggcca ccaaagtctc caagtcgact ggctgcatga aagccggatcttattgccgc 180 tctactacga gaacttgctg cggttattgc gcttatttcg gcaaaaaatgtattgactat 240 cccagcaact gatcttcccc ctactgtgct ctatcctttt ctgcctaagtcctccttacc 300 tgagagtggt catgaaccac tcatcaccct actcctctgg aggcccagaggagctacatt 360 gaaataaaag ccgcattgc 379 97 77 PRT Conus circumcisus 97Met Lys Leu Thr Cys Val Val Ile Val Ala Val Leu Leu Leu Thr Thr 1 5 1015 Cys Gln Leu Ile Thr Ala Asp Asp Ser Arg Gly Thr Gln Lys His Arg 20 2530 Ser Leu Thr Ser Ala Thr Lys Val Ser Lys Ser Thr Gly Cys Met Lys 35 4045 Ala Gly Ser Tyr Cys Arg Ser Thr Thr Arg Thr Cys Cys Gly Tyr Cys 50 5560 Ala Tyr Phe Gly Lys Lys Cys Ile Asp Tyr Pro Ser Asn 65 70 75 98 35PRT Conus circumcisus PEPTIDE (1)..(35) Xaa at residue 33 is Pro or Hyp;Xaa at residue 10, 21, 24 and 32 is Tyr, 125I-Tyr, mono-iodo-Tyr,di-iodo-Tyr, O-sulpho-Tyr or O-phospho-Tyr 98 Ser Thr Gly Cys Met LysAla Gly Ser Xaa Cys Arg Ser Thr Thr Arg 1 5 10 15 Thr Cys Cys Gly XaaCys Ala Xaa Phe Gly Lys Lys Cys Ile Asp Xaa 20 25 30 Xaa Ser Asn 35 99362 DNA Conus consors 99 atgaaactga cgtgtgtggt gatcgtcgcc gtgctgctcctgacggcctg tcaactcctc 60 acagctgatg actccagagg tacgcagaag catcgtgccctgaagtctta caccaaactc 120 tccatgttaa ctttgcgctg cgcatcttac ggaaaaccttgtggtattga caacgactgc 180 tgcaatacat gcgatccagc cagaaagaca tgtacgtagctgatccggcg tctgatcttc 240 ccccttctgt gctctatcct tttctgcctg agtcctccttacctgagagt ggtcatgaac 300 cactcatcac ctagctcctc tggaggcttc agaggagctacaatgaaata aaagcgcatt 360 gc 362 100 72 PRT Conus consors 100 Met LysLeu Thr Cys Val Val Ile Val Ala Val Leu Leu Leu Thr Ala 1 5 10 15 CysGln Leu Leu Thr Ala Asp Asp Ser Arg Gly Thr Gln Lys His Arg 20 25 30 AlaLeu Lys Ser Tyr Thr Lys Leu Ser Met Leu Thr Leu Arg Cys Ala 35 40 45 SerTyr Gly Lys Pro Cys Gly Ile Asp Asn Asp Cys Cys Asn Thr Cys 50 55 60 AspPro Ala Arg Lys Thr Cys Thr 65 70 101 26 PRT Conus consors PEPTIDE(1)..(26) Xaa at residue 7 and 20 is Pro or Hyp; Xaa at residue 4 isTyr, 125I-Tyr, mono-iodo-Tyr, di-iodo- Tyr, O-sulpho-Tyr orO-phospho-Tyr 101 Cys Ala Ser Xaa Gly Lys Xaa Cys Gly Ile Asp Asn AspCys Cys Asn 1 5 10 15 Thr Cys Asp Xaa Ala Arg Lys Thr Cys Thr 20 25 102237 DNA Conus consors 102 atgaaactga cgtgtgtggt gatcgtcgcc gtgctgctcctgacggcctg tcaactcctc 60 acagctgatg actccagagg tacgcagaag catcgtgccctgaggtcgga caccaaactc 120 tccatgtcga ctcgctgcaa gggtacagga aaaccatgcagtaggattgc gtataactgc 180 tgcaccggtt cttgcagatc aggtaaatgt ggctgatccagcgcctgatc tcccccc 237 103 71 PRT Conus consors 103 Met Lys Leu Thr CysVal Val Ile Val Ala Val Leu Leu Leu Thr Ala 1 5 10 15 Cys Gln Leu LeuThr Ala Asp Asp Ser Arg Gly Thr Gln Lys His Arg 20 25 30 Ala Leu Arg SerAsp Thr Lys Leu Ser Met Ser Thr Arg Cys Lys Gly 35 40 45 Thr Gly Lys ProCys Ser Arg Ile Ala Tyr Asn Cys Cys Thr Gly Ser 50 55 60 Cys Arg Ser GlyLys Cys Gly 65 70 104 25 PRT Conus consors PEPTIDE (1)..(25) Xaa atresidue 7 is Pro or Hyp; Xaa at residue 13 is Tyr, 125I-Tyr,mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr or O-phospho-Tyr 104 Cys LysGly Arg Gly Lys Xaa Cys Ser Arg Ile Ala Xaa Asn Cys Cys 1 5 10 15 ThrGly Ser Cys Arg Ser Gly Lys Cys 20 25 105 320 DNA Conus consors 105atgaaactga cgtgtgtggt gatcgtcgcc gtgctgctcc tgacggcctg tcaactcatc 60acagctgatg actccaaagg tacgcagaag catcgttccc tgaggtcgac caccaaagtc 120tccaaggcga ctgactgcat tgaagccgga aattattgcg gacctactgt tatgaaaatc 180tgctgcggct tttgcagtcc atacagcaaa atatgtatga actatcccca aaattgatct 240tcccccttct gtgctctatc cttttctgcc tgagtcctcc ttacctgaga gtggtcatga 300accactcatc acctcgtccc 320 106 78 PRT Conus consors 106 Met Lys Leu ThrCys Val Val Ile Val Ala Val Leu Leu Leu Thr Ala 1 5 10 15 Cys Gln LeuIle Thr Ala Asp Asp Ser Lys Gly Thr Gln Lys His Arg 20 25 30 Ser Leu ArgSer Thr Thr Lys Val Ser Lys Ala Thr Asp Cys Ile Glu 35 40 45 Ala Gly AsnTyr Cys Gly Pro Thr Val Met Lys Ile Cys Cys Gly Phe 50 55 60 Cys Ser ProTyr Ser Lys Ile Cys Met Asn Tyr Pro Gln Asn 65 70 75 107 36 PRT Conusconsors PEPTIDE (1)..(36) Xaa at residue 6 is Glu or gamma-carboxy Glu;Xaa at residue 13, 25 and 34 is Pro or Hyp; Xaa at residue 10, 26 and 33is Tyr, 125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr, O-sulpho- Tyr orO-phospho-Tyr 107 Ala Thr Asp Cys Ile Xaa Ala Gly Asn Xaa Cys Gly XaaThr Val Met 1 5 10 15 Lys Ile Cys Cys Gly Phe Cys Ser Xaa Xaa Ser LysIle Cys Met Asn 20 25 30 Xaa Xaa Gln Asn 35 108 321 DNA Conus consors108 atgaaactga cgtgtgtggt gatcgtcgcc gtgctgctcc tgacggcctg tcaactcctc 60acagctgatg actccagagg tacgcagaag catcgtgccc tgaggtcgga caccaaactc 120tccatgtcga ctcgctgcaa aggtaaagga gcatcatgta caaggcttat gtatgactgc 180tgccacggtt cttgcagcag cagcaagggt agatgtggct gatccggcgc ctgatcttcc 240cccttctgtg ctctatcctt ttctgcctga gtcctcctta cctgagaggt ggtcatgaac 300cactcatcac ctgctcccct g 321 109 73 PRT Conus consors 109 Met Lys Leu ThrCys Val Val Ile Val Ala Val Leu Leu Leu Thr Ala 1 5 10 15 Cys Gln LeuLeu Thr Ala Asp Asp Ser Arg Gly Thr Gln Lys His Arg 20 25 30 Ala Leu ArgSer Asp Thr Lys Leu Ser Met Ser Thr Arg Cys Lys Gly 35 40 45 Lys Gly AlaSer Cys Thr Arg Leu Met Tyr Asp Cys Cys His Gly Ser 50 55 60 Cys Ser SerSer Lys Gly Arg Cys Gly 65 70 110 27 PRT Conus consors PEPTIDE (1)..(27)Xaa at residue 13 is Tyr, 125I-Tyr, mono- iodo-Tyr, di-iodo-Tyr,O-sulpho-Tyr or O-phospho-Tyr 110 Cys Lys Gly Lys Gly Ala Ser Cys ThrArg Leu Met Xaa Asp Cys Cys 1 5 10 15 His Gly Ser Cys Ser Ser Ser LysGly Arg Cys 20 25 111 292 DNA Conus consors 111 ggatccatga aactgacgtgcatggtgatc gtcgccgtgc tgctcctgac ggcctgtcaa 60 ctcatcacag ctgatgactccagaggtacg cagaagcatc gtgccctgag gtcggacacc 120 aaactctcca tgtcaactcgctgcaagggt aaaggagcat catgtcatag gacttcgtat 180 gactgctgca ccggttcttgcaacagaggt aaatgtggct gatccggcgc ctgatcttcc 240 cccttctgtg ctctatccttttctgcctga gtcatccata cctgtgctcg ag 292 112 71 PRT Conus consors 112 MetLys Leu Thr Cys Met Val Ile Val Ala Val Leu Leu Leu Thr Ala 1 5 10 15Cys Gln Leu Ile Thr Ala Asp Asp Ser Arg Gly Thr Gln Lys His Arg 20 25 30Ala Leu Arg Ser Asp Thr Lys Leu Ser Met Ser Thr Arg Cys Lys Gly 35 40 45Lys Gly Ala Ser Cys His Arg Thr Ser Tyr Asp Cys Cys Thr Gly Ser 50 55 60Cys Asn Arg Gly Lys Cys Gly 65 70 113 25 PRT Conus consors PEPTIDE(1)..(25) Xaa at residue 13 is Tyr, 125I-Tyr, mono- iodo-Tyr,di-iodo-Tyr, O-sulpho-Tyr or O-phospho-Tyr 113 Cys Lys Gly Lys Gly AlaSer Cys His Arg Thr Ser Xaa Asp Cys Cys 1 5 10 15 Thr Gly Ser Cys AsnArg Gly Lys Cys 20 25 114 299 DNA Conus consors 114 ggatccatgaaactgacgtg cgtggtgatc gtcgccgtgc tgctcctgac ggcctgtcaa 60 ctcatcacagctgatgactc cagaggtacg cagaagcatc gtgccctgaa gtcggacacc 120 aaactctccatgttaacttt gcgctgcgca tcttacggaa aaccttgtgg tatttacaac 180 gactgctgcaatacatgcga tccagccaga aagacatgta cgtagctgat ccggcgtctg 240 atcttcccccttctgtgctc tatccttttc tgcctgagtc atccatacct gtgctcgag 299 115 72 PRTConus consors 115 Met Lys Leu Thr Cys Val Val Ile Val Ala Val Leu LeuLeu Thr Ala 1 5 10 15 Cys Gln Leu Ile Thr Ala Asp Asp Ser Arg Gly ThrGln Lys His Arg 20 25 30 Ala Leu Lys Ser Asp Thr Lys Leu Ser Met Leu ThrLeu Arg Cys Ala 35 40 45 Ser Tyr Gly Lys Pro Cys Gly Ile Tyr Asn Asp CysCys Asn Thr Cys 50 55 60 Asp Pro Ala Arg Lys Thr Cys Thr 65 70 116 26PRT Conus consors PEPTIDE (1)..(26) Xaa at residue 7 and 20 is Pro orHyp; Xaa at residue 4 and 11 is Tyr, 125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr or O-phospho-Tyr 116 Cys Ala Ser Xaa Gly Lys Xaa CysGly Ile Xaa Asn Asp Cys Cys Asn 1 5 10 15 Thr Cys Asp Xaa Ala Arg LysThr Cys Thr 20 25 117 434 DNA Conus consors misc_feature (1)..(434) nmay be any nucleotide 117 ggatccatga aactgacgtg tgtggtgatc gtcgccgtgctgctcctgac ggcctgtcaa 60 ctcatcacag ctgatgactc cagaggtacg cagaagcatcgtgccctgag gtcggacacc 120 aaactctcca tgtcgactcg ctgcaagggt acaggaaaaccatgcagtag ggttgcgtat 180 aactgctgca ccggttcttg cagatcaggt aaatgtggctgatccagtgc ctgatcttcc 240 cccttctgtg ctctatcctt ttctgcctga gtcctccttacctgagagtg gtcatgaacc 300 actcatcacc tgctcctctg gaggcttcag aggagctacattgaaataaa agccgcattg 360 cantgnanaa aannnnnnnn nnnnnnnnnn nnnnnnnnnnnnnnnnnnnn nnggaaaaaa 420 aaaaaaaaaa aaaa 434 118 71 PRT Conus consors118 Met Lys Leu Thr Cys Val Val Ile Val Ala Val Leu Leu Leu Thr Ala 1 510 15 Cys Gln Leu Ile Thr Ala Asp Asp Ser Arg Gly Thr Gln Lys His Arg 2025 30 Ala Leu Arg Ser Asp Thr Lys Leu Ser Met Ser Thr Arg Cys Lys Gly 3540 45 Thr Gly Lys Pro Cys Ser Arg Val Ala Tyr Asn Cys Cys Thr Gly Ser 5055 60 Cys Arg Ser Gly Lys Cys Gly 65 70 119 25 PRT Conus consors PEPTIDE(1)..(25) Xaa at residue 7 is Pro or Hyp; Xaa at residue 13 is Tyr,125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr or O-phospho-Tyr 119Cys Lys Gly Thr Gly Lys Xaa Cys Ser Arg Val Ala Xaa Asn Cys Cys 1 5 1015 Thr Gly Ser Cys Arg Ser Gly Lys Cys 20 25 120 393 DNA Conus consors120 ggatccatga aactgacgtg catggtgatc gtcgccgtgc tgctcctgac ggcctgtcaa 60ctcatcacag ctgatgactc cagaggtacg cagaagcatc gttccctgag gtcgaccacc 120aaagtctcca agtcgactag ctgcatgaaa gccgggtctt attgccgctc tactacgaga 180acctgctgcg gttattgcgc ttatttcggc aaattttgta ttgactttcc cagcaactga 240tcttccccct actgtgctct atccttttct gcctctgcct gagtcctcct tacctgagag 300tggtcatgaa ccactcatca cctgctcccc tggaggcctc agaggagcta caatgaaata 360aaagccgcat tgcaaaaaaa aaaaaaaaaa aaa 393 121 77 PRT Conus consors 121Met Lys Leu Thr Cys Met Val Ile Val Ala Val Leu Leu Leu Thr Ala 1 5 1015 Cys Gln Leu Ile Thr Ala Asp Asp Ser Arg Gly Thr Gln Lys His Arg 20 2530 Ser Leu Arg Ser Thr Thr Lys Val Ser Lys Ser Thr Ser Cys Met Lys 35 4045 Ala Gly Ser Tyr Cys Arg Ser Thr Thr Arg Thr Cys Cys Gly Tyr Cys 50 5560 Ala Tyr Phe Gly Lys Phe Cys Ile Asp Phe Pro Ser Asn 65 70 75 122 35PRT Conus consors PEPTIDE (1)..(35) Xaa at residue 33 is Pro or Hyp; Xaaat residue 10, 21 and 24 is Tyr, 125I-Tyr, mono-iodo-Tyr, di- iodo-Tyr,O-sulpho-Tyr or O-phospho-Tyr 122 Ser Thr Ser Cys Met Lys Ala Gly SerXaa Cys Arg Ser Thr Thr Arg 1 5 10 15 Thr Cys Cys Gly Xaa Cys Ala XaaPhe Gly Lys Phe Cys Ile Asp Phe 20 25 30 Xaa Ser Asn 35 123 361 DNAConus dalli 123 accaaaacca tcatcaaaat gaaactgacg tgtgtggtga tcgtcgccgtgctgttcctg 60 acggcctgtc aactcatcac agctgatgac tccagaagta cgcagaagcatcgtgctctg 120 aggtcgacca tcaaacactc catgttgact aggagctgca cgcctcccggaggaccttgt 180 ggttattata atgactgctg cagtcatcaa tgcaatataa gcagaaataaatgcgagtag 240 ctgatccggc atctgatctt ccccttctgt gctcgtccta acctgagagtggtcatgaac 300 catcatcacc tactcctctg gaggcttcag aggagctaca tggaaataaaagccgcattg 360 c 361 124 73 PRT Conus dalli 124 Met Lys Leu Thr Cys ValVal Ile Val Ala Val Leu Phe Leu Thr Ala 1 5 10 15 Cys Gln Leu Ile ThrAla Asp Asp Ser Arg Ser Thr Gln Lys His Arg 20 25 30 Ala Leu Arg Ser ThrIle Lys His Ser Met Leu Thr Arg Ser Cys Thr 35 40 45 Pro Pro Gly Gly ProCys Gly Tyr Tyr Asn Asp Cys Cys Ser His Gln 50 55 60 Cys Asn Ile Ser ArgAsn Lys Cys Glu 65 70 125 28 PRT Conus dalli PEPTIDE (1)..(28) Xaa atresidue 28 is Glu or gamma-carboxy Glu; Xaa at residue 4, 5 and 8 is Proor Hyp; Xaa at residue 11 and 12 is Tyr, 125I-Tyr, mono-iodo-Tyr,di-iodo-Tyr, O-sulpho-Tyr or O-phospho-Tyr 125 Ser Cys Thr Xaa Xaa GlyGly Xaa Cys Gly Xaa Xaa Asn Asp Cys Cys 1 5 10 15 Ser His Gln Cys AsnIle Ser Arg Asn Lys Cys Xaa 20 25 126 350 DNA Conus distans 126accaaaacca tcatcaaaat gaaactgacg tgcgtgttga tcatcgccgt gctgttcctg 60acggcctgtc aactcactag aggaaagctg gagcgtcctg ttctgaggtc gagcgaccaa 120acctccgggt caacgaagag atgcgaagat cctggtgaac cttgcggaag tgatcattcc 180tgctgcggcg gtagttgcaa ccacaacgtc tgcgcctgaa gctggtctgg catctgacca 240ttccccttct gtactctatc tctattgcct gagtcatctt tacctgtgag tggtcatgaa 300tctctcaata ccttctcccc tggaggcttc agaagaacta gattgaaata 350 127 66 PRTConus distans 127 Met Lys Leu Thr Cys Val Leu Ile Ile Ala Val Leu PheLeu Thr Ala 1 5 10 15 Cys Gln Leu Thr Arg Gly Lys Leu Glu Arg Pro ValLeu Arg Ser Ser 20 25 30 Asp Gln Thr Ser Gly Ser Thr Lys Arg Cys Glu AspPro Gly Glu Pro 35 40 45 Cys Gly Ser Asp His Ser Cys Cys Gly Gly Ser CysAsn His Asn Val 50 55 60 Cys Ala 65 128 25 PRT Conus distans PEPTIDE(1)..(25) Xaa at residue 2 and 6 is Glu or gamma-carboxy Glu; Xaa atresidue 4 and 7 is Pro or Hyp 128 Cys Xaa Asp Xaa Gly Xaa Xaa Cys GlySer Asp His Ser Cys Cys Gly 1 5 10 15 Gly Ser Cys Asn His Asn Val CysAla 20 25 129 309 DNA Conus ermineus 129 atgaaactga cgtgtgtggtgatcgtcgcc gtgctgctcc tgacggcctg tcaactcatc 60 acagctgacg actccagacgtacgcagaag catcgtgccc tgaggtcgac caccaaacgc 120 gccacgtcga atcgcccctgcaagccgaaa ggacgaaaat gttttccgca tcagaaggac 180 tgctgcaata aaacgtgcaccagatcaaaa tgtccctgat cttccccctt ctgtgctgta 240 tccttttctg cctgagtcctccttacctga gagtggtcag taaccactca tcaccatctc 300 ctctggagg 309 130 72 PRTConus ermineus 130 Met Lys Leu Thr Cys Val Val Ile Val Ala Val Leu LeuLeu Thr Ala 1 5 10 15 Cys Gln Leu Ile Thr Ala Asp Asp Ser Arg Arg ThrGln Lys His Arg 20 25 30 Ala Leu Arg Ser Thr Thr Lys Arg Ala Thr Ser AsnArg Pro Cys Lys 35 40 45 Pro Lys Gly Arg Lys Cys Phe Pro His Gln Lys AspCys Cys Asn Lys 50 55 60 Thr Cys Thr Arg Ser Lys Cys Pro 65 70 131 27PRT Conus ermineus PEPTIDE (1)..(27) Xaa at residue 1, 4, 11 and 27 isPro or Hyp 131 Xaa Xaa Lys Xaa Lys Gly Arg Lys Cys Phe Xaa His Gln LysAsp Cys 1 5 10 15 Cys Asn Lys Thr Cys Thr Arg Ser Lys Cys Xaa 20 25 132308 DNA Conus ermineus 132 aactcatcac agctgatgac tccagaggta cgcagaacgatcgtgccctg aggtcgacca 60 ccaaactctc catgctgact cgggcctgct ggtcttccggaacaccttgt ggtactgata 120 gtttatgctg cggtggatgc aatgtatcca aaagtaaatgtaactagctg attcggcgtc 180 tgaacttccc ccttctgtgc tctatccttt tctgcccgagtcctccatac ctgagaatgg 240 tcatgaacca ctcatcacct actcctctgg agacctcagaagagctacac tgaaataaaa 300 gcgcttgc 308 133 54 PRT Conus ermineus 133 LeuIle Thr Ala Asp Asp Ser Arg Gly Thr Gln Asn Asp Arg Ala Leu 1 5 10 15Arg Ser Thr Thr Lys Leu Ser Met Leu Thr Arg Ala Cys Trp Ser Ser 20 25 30Gly Thr Pro Cys Gly Thr Asp Ser Leu Cys Cys Gly Gly Cys Asn Val 35 40 45Ser Lys Ser Lys Cys Asn 50 134 27 PRT Conus ermineus PEPTIDE (1)..(27)Xaa at 8 residue is Pro or Hyp; Xaa at residue 3 is Trp or Bromo Trp 134Ala Cys Xaa Ser Ser Gly Thr Xaa Cys Gly Thr Asp Ser Leu Cys Cys 1 5 1015 Gly Gly Cys Asn Val Ser Lys Ser Lys Cys Asn 20 25 135 385 DNA Conusgeographus 135 ggatccatga aactgacgtg cgtggtgatc gtcgccgtgc tgctcctgacggcctgtcaa 60 ctcatcacag ctgatgactc cagaggtacg cagaagcatc gtgccctggggtcgaccacc 120 gaactctcct tgtcgactcg ctgcaagtca cccggatctt catgttcaccgactagttat 180 aattgctgca ggtcttgcaa tccatacgcc aaaagatgtt acggctaatccagcgcctga 240 tcttccccct tctgtgctct atcccttcct gtctgagtcc tccttacctgagagtggtca 300 tgaaccactc ctcacctact tctctggagg cttcggagga gctacattgaaataaaagcc 360 gcattgtaaa aaaaaaaaaa aaaaa 385 136 73 PRT Conusgeographus 136 Met Lys Leu Thr Cys Val Val Ile Val Ala Val Leu Leu LeuThr Ala 1 5 10 15 Cys Gln Leu Ile Thr Ala Asp Asp Ser Arg Gly Thr GlnLys His Arg 20 25 30 Ala Leu Gly Ser Thr Thr Glu Leu Ser Leu Ser Thr ArgCys Lys Ser 35 40 45 Pro Gly Ser Ser Cys Ser Pro Thr Ser Tyr Asn Cys CysArg Ser Cys 50 55 60 Asn Pro Tyr Ala Lys Arg Cys Tyr Gly 65 70 137 27PRT Conus geographus PEPTIDE (1)..(27) Xaa at residue 4, 10 and 21 isPro or Hyp; Xaa at residue 13, 22 and 27 is Tyr, 125I-Tyr,mono-iodo-Tyr, di-iodo- Tyr, O-sulpho-Tyr or O-phospho-Tyr 137 Cys LysSer Xaa Gly Ser Ser Cys Ser Xaa Thr Ser Xaa Asn Cys Cys 1 5 10 15 ArgSer Cys Asn Xaa Xaa Ala Lys Arg Cys Xaa 20 25 138 396 DNA Conusgeographus 138 ggatccatga aactgacgtg tgtggtgatc gtcgccgtgc tgctcctgacggcctgtcaa 60 ctcatcacag ctgatgactc cagaggtacg cagaagcatc gtgccctgaggtcgtccacc 120 aaactcacct tgtcgactcg ctgcaaatca cccggaactc catgttcaaggggtatgcgt 180 gattgctgca cgccttgctt gttatacagc aacaaatgta ggcgctactaacccagcgcc 240 tgatcttccc ccttctgtgc tctattcctt tctgcctgag tcctccttacctgaaagtgg 300 tcatgaacca ctcatcacct acttctctgg aggcttcaga agagctacattgaaataaaa 360 gccgcattgc aatgacaaaa aaaaaaaaaa aaaaaa 396 139 74 PRTConus geographus 139 Met Lys Leu Thr Cys Val Val Ile Val Ala Val Leu LeuLeu Thr Ala 1 5 10 15 Cys Gln Leu Ile Thr Ala Asp Asp Ser Arg Gly ThrGln Lys His Arg 20 25 30 Ala Leu Arg Ser Ser Thr Lys Leu Thr Leu Ser ThrArg Cys Lys Ser 35 40 45 Pro Gly Thr Pro Cys Ser Arg Gly Met Arg Asp CysCys Thr Pro Cys 50 55 60 Leu Leu Tyr Ser Asn Lys Cys Arg Arg Tyr 65 70140 29 PRT Conus geographus PEPTIDE (1)..(29) Xaa at residue 4, 7 and 18is Pro or Hyp; Xaa at residue 22 and 29 is Tyr, 125I-Tyr, mono-iodo-Tyr,di-iodo-Tyr, O-sulpho-Tyr or O-phospho-Tyr 140 Cys Lys Ser Xaa Gly ThrXaa Cys Ser Arg Gly Met Arg Asp Cys Cys 1 5 10 15 Thr Xaa Cys Leu LeuXaa Ser Asn Lys Cys Arg Arg Xaa 20 25 141 407 DNA Conus geographus 141ggaattccgt ttctgcgctg cttcctttgg catcaccaaa accatcatca aaatgaaact 60gacgtgtgtg gtgatcgtcg ccgtgctgct cctgacggcc tgtcaactca tcacagctga 120tgactccaga ggtacgcaga agcatcgtgc cctggggtcg accaccgaac tctccttgtc 180gactcgctgc aagtcacccg gatcttcatg ttcaccgact agttataatt gctgcaggtc 240ttgcaatcca tacaccaaaa gatgttacgg ctaatccagc gcctgatctt ccctgctctg 300agtcctcctt acctgagagt ggtcatgaac cactcatcac ctacttctct aggcggttcg 360gaggagctac attgaaataa aagccgcatt gcaaaaaaaa aaaaaaa 407 142 73 PRT Conusgeographus 142 Met Lys Leu Thr Cys Val Val Ile Val Ala Val Leu Leu LeuThr Ala 1 5 10 15 Cys Gln Leu Ile Thr Ala Asp Asp Ser Arg Gly Thr GlnLys His Arg 20 25 30 Ala Leu Gly Ser Thr Thr Glu Leu Ser Leu Ser Thr ArgCys Lys Ser 35 40 45 Pro Gly Ser Ser Cys Ser Pro Thr Ser Tyr Asn Cys CysArg Ser Cys 50 55 60 Asn Pro Tyr Thr Lys Arg Cys Tyr Gly 65 70 143 27PRT Conus geographus PEPTIDE (1)..(27) Xaa at residue 4, 10 and 21 isPro or Hyp; Xaa at residue 13, 22 and 27 is Tyr, 125I-Tyr,mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr or O-phospho-Tyr 143 Cys LysSer Xaa Gly Ser Ser Cys Ser Xaa Thr Ser Xaa Asn Cys Cys 1 5 10 15 ArgSer Cys Asn Xaa Xaa Thr Lys Arg Cys Xaa 20 25 144 28 PRT Conusgeographus PEPTIDE (1)..(28) Xaa at residue 4, 10 and 21 is Pro or Hyp;Xaa at residue 13, 22 and 27 is Tyr, 125I-Tyr, mono-iodo-Tyr,di-iodo-Tyr, O-sulpho-Tyr or O-phospho-Tyr 144 Cys Lys Ser Xaa Gly SerSer Cys Ser Xaa Thr Ser Xaa Asn Cys Cys 1 5 10 15 Arg Ser Cys Asn XaaXaa Thr Lys Arg Cys Xaa Gly 20 25 145 26 PRT Conus geographus PEPTIDE(1)..(26) Xaa at residue 4, 10 and 21 is Pro or Hyp; Xaa at residue 13and 22 is Tyr, 125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr orO-phospho-Tyr 145 Cys Lys Ser Xaa Gly Ser Ser Cys Ser Xaa Thr Ser XaaAsn Cys Cys 1 5 10 15 Arg Ser Cys Asn Xaa Xaa Thr Lys Arg Cys 20 25 146314 DNA Conus geographus 146 catcacagct gatgactcca gaggtacgca gaagcatcgtgccctgaggt cgtccaccaa 60 actcaccttg tcgactcgct gcaaatcacc cggaactccatgttcaaggg gtatgcgtga 120 ttgctgcacg tcttgcttgt tatacagcaa caaatgtaggcgctactaac ccagcgcctg 180 atcttccccc ttctgtgctc tattcctttc tgcctgagtcctccttacct gaaagtggtc 240 atgaaccact catcacctac ttctctggag gcttcagaagagctacattg aaataaaagc 300 cgcattgcaa tgac 314 147 55 PRT Conusgeographus 147 Ile Thr Ala Asp Asp Ser Arg Gly Thr Gln Lys His Arg AlaLeu Arg 1 5 10 15 Ser Ser Thr Lys Leu Thr Leu Ser Thr Arg Cys Lys SerPro Gly Thr 20 25 30 Pro Cys Ser Arg Gly Met Arg Asp Cys Cys Thr Ser CysLeu Leu Tyr 35 40 45 Ser Asn Lys Cys Arg Arg Tyr 50 55 148 29 PRT Conusgeographus PEPTIDE (1)..(29) Xaa at residue 4 and 7 is Pro or Hyp; Xaaat residue 22 and 29 is Tyr, 125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr,O-sulpho-Tyr or O-phospho-Tyr 148 Cys Lys Ser Xaa Gly Thr Xaa Cys SerArg Gly Met Arg Asp Cys Cys 1 5 10 15 Thr Ser Cys Leu Leu Xaa Ser AsnLys Cys Arg Arg Xaa 20 25 149 29 PRT Conus geographus PEPTIDE (1)..(29)Xaa at residue 4 and 7 is Pro or Hyp; Xaa at residue 22 and 29 is Tyr,125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr or O-phospho-Tyr 149Cys Lys Ser Xaa Gly Thr Xaa Cys Ser Arg Gly Met Arg Asp Cys Cys 1 5 1015 Thr Ser Cys Leu Ser Xaa Ser Asn Lys Cys Arg Arg Xaa 20 25 150 380 DNAConus laterculatus 150 accaaaacca tcatcaaaat gaaactgacg tgtgtggtgatcgtcgccgt gctgctcctg 60 acggcctgtc aactcatcac cgctgatgac tccagaggtacgcagaagca tcgtgccctg 120 aggtcgacca ccaatctctc catgctgact cggaagtgctggccttccgg aagctattgt 180 cgtgcgaata gtaaatgctg cagtggatgc gatcggaacagaaataaatg ttactagctg 240 attcggcgtc tgaacttcct ccttctgtgc tctatccttttctgcccgag tcctccatac 300 ctgagagtgg tcatgaacca ctcaactcct actcctctggaggcctcaga agagctacat 360 tgaaataaaa gccgcattgc 380 151 72 PRT Conuslaterculatus 151 Met Lys Leu Thr Cys Val Val Ile Val Ala Val Leu Leu LeuThr Ala 1 5 10 15 Cys Gln Leu Ile Thr Ala Asp Asp Ser Arg Gly Thr GlnLys His Arg 20 25 30 Ala Leu Arg Ser Thr Thr Asn Leu Ser Met Leu Thr ArgLys Cys Trp 35 40 45 Pro Ser Gly Ser Tyr Cys Arg Ala Asn Ser Lys Cys CysSer Gly Cys 50 55 60 Asp Arg Asn Arg Asn Lys Cys Tyr 65 70 152 27 PRTConus laterculatus PEPTIDE (1)..(27) Xaa at residue 4 is Pro or Hyp; Xaaat residue 3 is Trp or Bromo Trp; Xaa at residue 8 and 27 is Tyr,125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr or O-phospho-Tyr 152Lys Cys Xaa Xaa Ser Gly Ser Xaa Cys Arg Ala Asn Ser Lys Cys Cys 1 5 1015 Ser Gly Cys Asp Arg Asn Arg Asn Lys Cys Xaa 20 25 153 367 DNA Conuslaterculatus 153 accaaaacca tcatcaaaat gaaactgacg tgtgtggtga tcgtcgccgtgctgctcctg 60 acggcctgtc aactcatcac agctgatgac tccagaggta cgcagaagcatcgtgccctg 120 aggtcgacca ccaaactctc catatcgact cgctgccttc ctcccggatcatattgtaag 180 gcgacaacgg aagtctgctg ctcttcttgc cttcaattcg ctcagatatgttcgggttga 240 tcttccctct tctgtgctct atccttttct gcctgagtcc tccatacctgagaatggtca 300 tgaaccactc aacatctact cctctggagg cctcagaaga gctatattgaaataaaagcc 360 gcattgc 367 154 73 PRT Conus laterculatus 154 Met Lys LeuThr Cys Val Val Ile Val Ala Val Leu Leu Leu Thr Ala 1 5 10 15 Cys GlnLeu Ile Thr Ala Asp Asp Ser Arg Gly Thr Gln Lys His Arg 20 25 30 Ala LeuArg Ser Thr Thr Lys Leu Ser Ile Ser Thr Arg Cys Leu Pro 35 40 45 Pro GlySer Tyr Cys Lys Ala Thr Thr Glu Val Cys Cys Ser Ser Cys 50 55 60 Leu GlnPhe Ala Gln Ile Cys Ser Gly 65 70 155 27 PRT Conus laterculatus PEPTIDE(1)..(27) Xaa at residue 13 is Glu or gamma-carboxy Glu; Xaa at residue3 and 4 is Pro or Hyp; Xaa at residue 7 is Tyr, 125I-Tyr, mono-iodo-Tyr,di-iodo-Tyr, O-sulpho-Tyr or O-phospho-Tyr 155 Cys Leu Xaa Xaa Gly SerXaa Cys Lys Ala Thr Thr Xaa Val Cys Cys 1 5 10 15 Ser Ser Cys Leu GlnPhe Ala Gln Ile Cys Ser 20 25 156 373 DNA Conus laterculatus 156accaaaacca tcatcaaaat gaaactgacg tgtgtggtga tcgtcgccgt gctgctcctg 60acggcctgtc aactcatcac agctgatgac tccagaggta cgcagaagca tcgtgccctg 120aggtcgacca ccaatctctc catgtcgact cgctgcaagt ctcccggatc atcatgtagc 180gtgtctatgc gtaactgctg cacttcttgc aattcacgca ccaagaaatg tacgcgacgt 240ggctgaactt cccccttctg tgctctatcc ttttctgccc gagtcctcca tacctgagag 300tggtcatgaa ccactcaaca tctactcctc tggaggcctc agaagagcta tattgaaata 360aaagccgcat tgc 373 157 75 PRT Conus laterculatus 157 Met Lys Leu Thr CysVal Val Ile Val Ala Val Leu Leu Leu Thr Ala 1 5 10 15 Cys Gln Leu IleThr Ala Asp Asp Ser Arg Gly Thr Gln Lys His Arg 20 25 30 Ala Leu Arg SerThr Thr Asn Leu Ser Met Ser Thr Arg Cys Lys Ser 35 40 45 Pro Gly Ser SerCys Ser Val Ser Met Arg Asn Cys Cys Thr Ser Cys 50 55 60 Asn Ser Arg ThrLys Lys Cys Thr Arg Arg Gly 65 70 75 158 29 PRT Conus laterculatusPEPTIDE (1)..(29) Xaa at residue 3 is Pro or Hyp 158 Cys Lys Ser Xaa GlySer Ser Cys Ser Val Ser Met Arg Asn Cys Cys 1 5 10 15 Thr Ser Cys AsnSer Arg Thr Lys Lys Cys Thr Arg Arg 20 25 159 330 DNA Conus laterculatus159 accaaaacca tcatcaaaat gaaactgacg tgtgtggtga tcgtcgccgt gctgctcctg 60acggcctgtc aactcatcac agctgatgac tccagaggta cgcagaagca tcgtgccctg 120aggtcgacaa ccaaactctc catgctgact cggacctgct ggccttccgg aacagcttgt 180ggtattgata gtaactgctg cagtggatgc aatgtatcca gaagtaaatg taactagctg 240attcggcgtc taaacttcct ccttctgcct gagtcctcca tacctgagag tggtcatgaa 300ccacatcatc acctcatctc tggaggcctc 330 160 72 PRT Conus laterculatus 160Met Lys Leu Thr Cys Val Val Ile Val Ala Val Leu Leu Leu Thr Ala 1 5 1015 Cys Gln Leu Ile Thr Ala Asp Asp Ser Arg Gly Thr Gln Lys His Arg 20 2530 Ala Leu Arg Ser Thr Thr Lys Leu Ser Met Leu Thr Arg Thr Cys Trp 35 4045 Pro Ser Gly Thr Ala Cys Gly Ile Asp Ser Asn Cys Cys Ser Gly Cys 50 5560 Asn Val Ser Arg Ser Lys Cys Asn 65 70 161 27 PRT Conus laterculatusPEPTIDE (1)..(27) Xaa at residue 4 is Pro or Hyp; Xaa at residue 3 isTrp or Bromo Trp 161 Thr Cys Xaa Xaa Ser Gly Thr Ala Cys Gly Ile Asp SerAsn Cys Cys 1 5 10 15 Ser Gly Cys Asn Val Ser Arg Ser Lys Cys Asn 20 25162 363 DNA Conus laterculatus 162 accaaaacca tcatcaaaat gaaactgacgtgtgtggtga tcgtcgccgt gctgctcctg 60 acggcctgtc aactcatcac agctgatgactccagaggta cgcagaagca tcgtgccctg 120 aggtcgacca ccaatctctc catgctgactcggaagtgct ggccttccgg aagctattgt 180 cgtgcgaata gtaaatgctg cagtggatgcgatcggaaca gaagtaaatg taactagctg 240 attcggcgtc taaacttcct ccttctgcctgagtcctcca tacctgagag tggtcatgaa 300 ccactcatca cctactcctc tggaggcctcaaaggagcta cattgaaata aaagccgcat 360 tgc 363 163 72 PRT Conuslaterculatus 163 Met Lys Leu Thr Cys Val Val Ile Val Ala Val Leu Leu LeuThr Ala 1 5 10 15 Cys Gln Leu Ile Thr Ala Asp Asp Ser Arg Gly Thr GlnLys His Arg 20 25 30 Ala Leu Arg Ser Thr Thr Asn Leu Ser Met Leu Thr ArgLys Cys Trp 35 40 45 Pro Ser Gly Ser Tyr Cys Arg Ala Asn Ser Lys Cys CysSer Gly Cys 50 55 60 Asp Arg Asn Arg Ser Lys Cys Asn 65 70 164 27 PRTConus laterculatus PEPTIDE (1)..(27) Xaa at residue4 is Pro or Hyp; Xaaat residue 3 is Trp or Bromo Trp; Xaa at residue 8 is Tyr, 125I-Tyr,mono- iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr or O-phospho-Tyr 164 Lys CysXaa Xaa Ser Gly Ser Xaa Cys Arg Ala Asn Ser Lys Cys Cys 1 5 10 15 SerGly Cys Asp Arg Asn Arg Ser Lys Cys Asn 20 25 165 391 DNA Conusleopardus misc_feature (1)..(391) n may be any nucleotide 165 atgaaactgacgtgtgtggt gatcgtagct gtgctgttcc tgacggcctg tcaactcact 60 acagctgacatctccagagg tacgcggaag cgtcgtgctc tgaggtcgac caccaaactc 120 tccaggtcgctctttgagtg cgcgccttcc ggtggacgtt gtggtttttt aaagtcctgc 180 tgcgaaggatattgcgatgg ggaaagcact tcatgtgtga gtggcccata cagcatctga 240 tcttcccgccttcagtgctc tatccttttc tgcctgagtc ctccatacct ctgagcggtc 300 atgaaccactcaacacctac tcctctggag gcttcaggga actatattaa aataaagccg 360 cattgcaacgaaanaaaaaa aaaaaaaaaa a 391 166 79 PRT Conus leopardus 166 Met Lys LeuThr Cys Val Val Ile Val Ala Val Leu Phe Leu Thr Ala 1 5 10 15 Cys GlnLeu Thr Thr Ala Asp Ile Ser Arg Gly Thr Arg Lys Arg Arg 20 25 30 Ala LeuArg Ser Thr Thr Lys Leu Ser Arg Ser Leu Phe Glu Cys Ala 35 40 45 Pro SerGly Gly Arg Cys Gly Phe Leu Lys Ser Cys Cys Glu Gly Tyr 50 55 60 Cys AspGly Glu Ser Thr Ser Cys Val Ser Gly Pro Tyr Ser Ile 65 70 75 167 37 PRTConus leopardus PEPTIDE (1)..(37) Xaa at residue 4, 20 and 26 is Glu orgamma- carboxy Glu; Xaa at residue 7 and 34 is Pro or Hyp; Xaa atresidue 22 and 35 is Tyr, 125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr,O-sulpho- Tyr or O-phospho-Tyr 167 Ser Leu Phe Xaa Cys Ala Xaa Ser GlyGly Arg Cys Gly Phe Leu Lys 1 5 10 15 Ser Cys Cys Xaa Gly Xaa Cys AspGly Xaa Ser Thr Ser Cys Val Ser 20 25 30 Gly Xaa Xaa Ser Ile 35 168 365DNA Conus leopardus 168 atgaaactga cgtgtgtggt gatcgtcgct gtgctgttcctgacggcctg tcaactcact 60 acagctgaca tctccagagg tacgtggaag catcgtggtgtggggtcgac caccggactc 120 tccccgtggc ccttggactg cacggctccc agtcaaccttgtggttattt tcctaggtgc 180 tgtggacatt gcgatgtacg cagggtatgt acgagtggctgatccggcgt ctgatctttc 240 cgccttctgt gctgtatcct tttctgcctg agtcctccatacccgtgagt ggtcatgaac 300 cactcaacac ctactcctct ggaggcttca gaggaactatattaaaataa agccgcattg 360 caatg 365 169 73 PRT Conus leopardus 169 MetLys Leu Thr Cys Val Val Ile Val Ala Val Leu Phe Leu Thr Ala 1 5 10 15Cys Gln Leu Thr Thr Ala Asp Ile Ser Arg Gly Thr Trp Lys His Arg 20 25 30Gly Val Gly Ser Thr Thr Gly Leu Ser Pro Trp Pro Leu Asp Cys Thr 35 40 45Ala Pro Ser Gln Pro Cys Gly Tyr Phe Pro Arg Cys Cys Gly His Cys 50 55 60Asp Val Arg Arg Val Cys Thr Ser Gly 65 70 170 30 PRT Conus leopardusPEPTIDE (1)..(30) Xaa at residue 2, 8, 11 and 16 is Pro or Hyp; Xaa atresidue 1 is Trp or Bromo Trp; Xaa at residue 14 is Tyr, 125I-Tyr,mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr or O-phospho- Tyr 170 Xaa XaaLeu Asp Cys Thr Ala Xaa Ser Gln Xaa Cys Gly Xaa Phe Xaa 1 5 10 15 ArgCys Cys Gly His Cys Asp Val Arg Arg Val Cys Thr Ser 20 25 30 171 381 DNAConus leopardus 171 atgaaactga cgtgtgtggt gatcgtcgct gtgctgttcctgacggcctg tcaactcact 60 acagctgaca tctccagagg tacgcggaag catcgtgctctgaggtcgac caccaaactc 120 tccaggtcgc cctctaggtg catgtctccc ggtggaatttgtggtgattt tggtgactgc 180 tgcgaaattt gcaatgtgta cggtatatgt gtgagtgacttacccggcat ctgatctttc 240 cgccttctgt gctctatcct tttctgcctg agtcctccatacccctgagt ggtcatggac 300 cactcaacac ctactcctct ggaggcttca gaggaactacattaaaataa agccgcattg 360 caaaaaaaaa aaaaaaaaaa a 381 172 77 PRT Conusleopardus 172 Met Lys Leu Thr Cys Val Val Ile Val Ala Val Leu Phe LeuThr Ala 1 5 10 15 Cys Gln Leu Thr Thr Ala Asp Ile Ser Arg Gly Thr ArgLys His Arg 20 25 30 Ala Leu Arg Ser Thr Thr Lys Leu Ser Arg Ser Pro SerArg Cys Met 35 40 45 Ser Pro Gly Gly Ile Cys Gly Asp Phe Gly Asp Cys CysGlu Ile Cys 50 55 60 Asn Val Tyr Gly Ile Cys Val Ser Asp Leu Pro Gly Ile65 70 75 173 31 PRT Conus leopardus PEPTIDE (1)..(31) Xaa at residue 16is Glu or gamma-carboxy Glu; Xaa at residue 4 and 29 is Pro or Hyp; Xaaat residue 21 is Tyr, 125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyror O-phospho-Tyr 173 Cys Met Ser Xaa Gly Gly Ile Cys Gly Asp Phe Gly AspCys Cys Xaa 1 5 10 15 Ile Cys Asn Val Xaa Gly Ile Cys Val Ser Asp LeuXaa Gly Ile 20 25 30 174 404 DNA Conus leopardus 174 atgaaactgacgtgtgtggt gatcgtcgct gtgctgttcc tgacggcctg tcaactcact 60 acagctgatgattccagagg tacacggaag catcgtgctc tgaggtcaac caccaaactc 120 tccaggtggcccaggtactg cgcgcctccc ggtggagctt gtgggttttt tgatcactgc 180 tgcggatattgcgaaacgtt ttacaatacg tgtagatgag ttggctgatc cggcgcttga 240 tctttccgccttctgttgct ctatcttttt ctgcctgagt cctcccatac cccgttgagt 300 ggtccatgaaccactccaac acctactccc tccttggaag cttccaaagg aaacgacatt 360 taaaataaattccccattgc aattggaaaa aaaaaaaaaa aaaa 404 175 72 PRT Conus leopardus 175Met Lys Leu Thr Cys Val Val Ile Val Ala Val Leu Phe Leu Thr Ala 1 5 1015 Cys Gln Leu Thr Thr Ala Asp Asp Ser Arg Gly Thr Arg Lys His Arg 20 2530 Ala Leu Arg Ser Thr Thr Lys Leu Ser Arg Trp Pro Arg Tyr Cys Ala 35 4045 Pro Pro Gly Gly Ala Cys Gly Phe Phe Asp His Cys Cys Gly Tyr Cys 50 5560 Glu Thr Phe Tyr Asn Thr Cys Arg 65 70 176 27 PRT Conus leopardusPEPTIDE (1)..(27) Xaa at residue 20 is Glu or gamma-carboxy Glu; Xaa atresidue 4 and 5 is Pro or Hyp; Xaa at residue 1, 18 and 23 is Tyr,125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr or O- phospho-Tyr 176Xaa Cys Ala Xaa Xaa Gly Gly Ala Cys Gly Phe Phe Asp His Cys Cys 1 5 1015 Gly Xaa Cys Xaa Thr Phe Xaa Asn Thr Cys Arg 20 25 177 292 DNA Conuslynceus 177 atgaaactga cgtgtgtggt gatcgtcgcc gtgctgctcc tgacggcctgtcaactcatc 60 acagctgatg actccagacg tacacagaag catcgtgccc tgaggtcgaccaccaatctc 120 tccatgtcga ctcgctgcaa gtctcccgga tcaccatgta gtgtgacatcgtataactgc 180 tgcacttttt gctcttcata cactaagaaa tgtcgggcct ctttatgaaccactcatcac 240 ctactcctct ggaggcctca gaagagctac actgaaataa aagccgcatt gg292 178 75 PRT Conus lynceus 178 Met Lys Leu Thr Cys Val Val Ile Val AlaVal Leu Leu Leu Thr Ala 1 5 10 15 Cys Gln Leu Ile Thr Ala Asp Asp SerArg Arg Thr Gln Lys His Arg 20 25 30 Ala Leu Arg Ser Thr Thr Asn Leu SerMet Ser Thr Arg Cys Lys Ser 35 40 45 Pro Gly Ser Pro Cys Ser Val Thr SerTyr Asn Cys Cys Thr Phe Cys 50 55 60 Ser Ser Tyr Thr Lys Lys Cys Arg AlaSer Leu 65 70 75 179 30 PRT Conus lynceus PEPTIDE (1)..(30) Xaa atresidue 4 and 7 is Pro or Hyp; Xaa at residue 13 and 22 is Tyr,125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr or O-phospho-Tyr 179Cys Lys Ser Xaa Gly Ser Xaa Cys Ser Val Thr Ser Xaa Asn Cys Cys 1 5 1015 Thr Phe Cys Ser Ser Xaa Thr Lys Lys Cys Arg Ala Ser Leu 20 25 30 180355 DNA Conus lynceus 180 atgaaactga cgtgtgtggt gatcgtcgcc gtgctgctcctgacggcctg tcaactcatc 60 acagctgatg actccagagg tacgcagaag catcgtgccctgaggtcgac caccaaacta 120 tccatgtata ctcgctgcgc aggtccagga gcaatttgtcctaatagggt atgctgcggt 180 tattgcagta aaagaacaca tctatgtcat tcgcgaactggctgatcttc ccccttctgt 240 gctctatcct ttttctgcct gagtcctcca tacctgagaatggtcatgaa ccactcatca 300 cctactcctc ttggagacct cagaggagct acactgaaataaaagccgca ttggc 355 181 74 PRT Conus lynceus 181 Met Lys Leu Thr CysVal Val Ile Val Ala Val Leu Leu Leu Thr Ala 1 5 10 15 Cys Gln Leu IleThr Ala Asp Asp Ser Arg Gly Thr Gln Lys His Arg 20 25 30 Ala Leu Arg SerThr Thr Lys Leu Ser Met Tyr Thr Arg Cys Ala Gly 35 40 45 Pro Gly Ala IleCys Pro Asn Arg Val Cys Cys Gly Tyr Cys Ser Lys 50 55 60 Arg Thr His LeuCys His Ser Arg Thr Gly 65 70 182 28 PRT Conus lynceus PEPTIDE (1)..(28)Xaa at residue 4 and 9 is Pro or Hyp; Xaa at residue 16 is Tyr,125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr, O-sulpho- Tyr or O-phospho-Tyr 182Cys Ala Gly Xaa Gly Ala Ile Cys Xaa Asn Arg Val Cys Cys Gly Xaa 1 5 1015 Cys Ser Lys Arg Thr His Leu Cys His Ser Arg Thr 20 25 183 361 DNAConus lynceus 183 atgaaactga cgtgtgtggt gatcgtcgcc gtgctgctgc tagcggcctgtcaactacta 60 cacgctgatg actccagagg tacgcagaag actgctgccc gaggtcgaccaccaaaactc 120 tccatgctga ctcgggcctg ctggtcttcc ggaacacctt gtggtactgatagtttatgc 180 tgcggtggat gcaatgtatc caaaagtaaa tgtaactagc tgattcggcgtctgaacttc 240 ccccttctgt gctctatcct tttctgcccg agtcctccat acctgagaatggtcatgaac 300 cactcatcac ctactcctct ggagacctca gaagagctac actgaaataaaagcgcattg 360 c 361 184 72 PRT Conus lynceus 184 Met Lys Leu Thr CysVal Val Ile Val Ala Val Leu Leu Leu Ala Ala 1 5 10 15 Cys Gln Leu LeuHis Ala Asp Asp Ser Arg Gly Thr Gln Lys Thr Ala 20 25 30 Ala Arg Gly ArgPro Pro Lys Leu Ser Met Leu Thr Arg Ala Cys Trp 35 40 45 Ser Ser Gly ThrPro Cys Gly Thr Asp Ser Leu Cys Cys Gly Gly Cys 50 55 60 Asn Val Ser LysSer Lys Cys Asn 65 70 185 27 PRT Conus lynceus PEPTIDE (1)..(27) Xaa atresidue 8 is Pro or Hyp; Xaa at residue 3 is Trp or Bromo Trp 185 AlaCys Xaa Ser Ser Gly Thr Xaa Cys Gly Thr Asp Ser Leu Cys Cys 1 5 10 15Gly Gly Cys Asn Val Ser Lys Ser Lys Cys Asn 20 25 186 364 DNA Conuslynceus 186 atgaaactga cgtgtgtggt gatcgtcgcc gagctactcc taacggcctgtcaactcatc 60 acagctgatg actccagagg tacgcagaag catcgtgccc tgaggtcgaccaccaatctc 120 tccatgctga ctcggaagtg ctggtctccc ggaacctatt gtcgtgcgcatagtaaatgc 180 tgccgtggat gcgatcagaa cagaaataaa tgttactagc tgattcggcgtctgaacttc 240 ctccttctgt gctctatcct ttttctgcct gagtcctcca tacctgagaatggtcatgaa 300 ccactcatca cctactcctc tggaggcctc agaggagcct acactgaaataaaagccgca 360 ttgg 364 187 72 PRT Conus lynceus 187 Met Lys Leu Thr CysVal Val Ile Val Ala Glu Leu Leu Leu Thr Ala 1 5 10 15 Cys Gln Leu IleThr Ala Asp Asp Ser Arg Gly Thr Gln Lys His Arg 20 25 30 Ala Leu Arg SerThr Thr Asn Leu Ser Met Leu Thr Arg Lys Cys Trp 35 40 45 Ser Pro Gly ThrTyr Cys Arg Ala His Ser Lys Cys Cys Arg Gly Cys 50 55 60 Asp Gln Asn ArgAsn Lys Cys Tyr 65 70 188 27 PRT Conus lynceus PEPTIDE (1)..(27) Xaa atresidue 5 is Pro or Hyp; Xaa at residue 3 is Trp or Bromo Trp; Xaa atresidue 8 and 27 is Tyr, 125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr,O-sulpho-Tyr or O-phospho-Tyr 188 Lys Cys Xaa Ser Xaa Gly Thr Xaa CysArg Ala His Ser Lys Cys Cys 1 5 10 15 Arg Gly Cys Asp Gln Asn Arg AsnLys Cys Xaa 20 25 189 318 DNA Conus magus 189 accaaaacca tcatcaaaatgaaactgacg tgtgtggtga tcgtcgccgt gctgctcctg 60 acggcctgtc aactcatcacagctgatgac tccagaggta cgcagaagca tcgtgccctg 120 aggtcggaca ccaaactctccatgtcgact cgctgcaagg gtacaggaaa accatgcagt 180 aggattgcgt ataactgctgcaccggttct tgcagatcag gtaaatgtgg ctgatccagt 240 gcctgatctt cccccttctgtgctctatcc tttttctgcc tgagtcctcc ttacctgaga 300 gtggtcatga accactca 318190 71 PRT Conus magus 190 Met Lys Leu Thr Cys Val Val Ile Val Ala ValLeu Leu Leu Thr Ala 1 5 10 15 Cys Gln Leu Ile Thr Ala Asp Asp Ser ArgGly Thr Gln Lys His Arg 20 25 30 Ala Leu Arg Ser Asp Thr Lys Leu Ser MetSer Thr Arg Cys Lys Gly 35 40 45 Thr Gly Lys Pro Cys Ser Arg Ile Ala TyrAsn Cys Cys Thr Gly Ser 50 55 60 Cys Arg Ser Gly Lys Cys Gly 65 70 19125 PRT Conus magus PEPTIDE (1)..(25) Xaa at residue 7 is Pro or Hyp; Xaaat residue 13 is Tyr, 125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyror O-phospho-Tyr 191 Cys Lys Gly Thr Gly Lys Xaa Cys Ser Arg Ile Ala XaaAsn Cys Cys 1 5 10 15 Thr Gly Ser Cys Arg Ser Gly Lys Cys 20 25 192 259DNA Conus magus 192 accaaaacca tcatcaaaat gaaactgacg tgtgtggtgatcgtcgccgt gctgctcctg 60 acggcctgtc aactcatcac agctgatgac tccagaggtacgcagaagca tcgtgccctg 120 aagtcggaca ccaaactctc catgttaact ttgcgctgcgcatcttacgg aaaaccttgt 180 ggtatttaca acgactgctg caatacatgc gatccagccagaaagacatg tacgtagctg 240 atccggcgtc tgatcttcc 259 193 72 PRT Conusmagus 193 Met Lys Leu Thr Cys Val Val Ile Val Ala Val Leu Leu Leu ThrAla 1 5 10 15 Cys Gln Leu Ile Thr Ala Asp Asp Ser Arg Gly Thr Gln LysHis Arg 20 25 30 Ala Leu Lys Ser Asp Thr Lys Leu Ser Met Leu Thr Leu ArgCys Ala 35 40 45 Ser Tyr Gly Lys Pro Cys Gly Ile Tyr Asn Asp Cys Cys AsnThr Cys 50 55 60 Asp Pro Ala Arg Lys Thr Cys Thr 65 70 194 26 PRT Conusmagus PEPTIDE (1)..(26) Xaa at residue 7 and 20 is Pro or Hyp; Xaa atresidue 4 and 11 is Tyr, 125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr or O-phospho-Tyr 194 Cys Ala Ser Xaa Gly Lys Xaa Cys Gly IleXaa Asn Asp Cys Cys Asn 1 5 10 15 Thr Cys Asp Xaa Ala Arg Lys Thr CysThr 20 25 195 254 DNA Conus magus 195 gaattttcag catcaccaaa accatcatcaaaatgaaact gacgtgtgtg gtgatcgtcg 60 ccgtgctgct cctgacggcc tgtcaactcatcacagctga tgactccaga ggtacgcaga 120 agcatcgtgc cctgaggtcg gacaccaaactctccatgtc aactcgctgc aagggtaaag 180 gagcatcatg tcataggact tcgtatgactgctgcaccgg ttcttgcaac agaggtaaat 240 ttggctgatc cgcc 254 196 71 PRTConus magus 196 Met Lys Leu Thr Cys Val Val Ile Val Ala Val Leu Leu LeuThr Ala 1 5 10 15 Cys Gln Leu Ile Thr Ala Asp Asp Ser Arg Gly Thr GlnLys His Arg 20 25 30 Ala Leu Arg Ser Asp Thr Lys Leu Ser Met Ser Thr ArgCys Lys Gly 35 40 45 Lys Gly Ala Ser Cys His Arg Thr Ser Tyr Asp Cys CysThr Gly Ser 50 55 60 Cys Asn Arg Gly Lys Phe Gly 65 70 197 25 PRT Conusmagus PEPTIDE (1)..(25) Xaa at residue 13 is Tyr, 125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr or O-phospho-Tyr 197 Cys Lys Gly Lys GlyAla Ser Cys His Arg Thr Ser Xaa Asp Cys Cys 1 5 10 15 Thr Gly Ser CysAsn Arg Gly Lys Cys 20 25 198 358 DNA Conus miles 198 ggatccatgaaactgacgtg cgtggtgatc atcgccatgc tgttcctgac agcctatcaa 60 ctcgctacagctgcgagcta cgccaaaggt aaacagaagc atcgtgctct gaggccagct 120 gacaaacacctcaggttgac caagcgttgc aatgatcgcg gtggaggttg cagtcaacat 180 cctcactgctgcggtggaac ttgcaataag cttattggcg tatgtctgta aagctggtct 240 gccgtctgatattccctttc tgtgcttcat cctcttttgc ctgagtcatc catacctgtg 300 aatggttaagagccactcaa tacctattcc tctgggggct tcagaggaac tactttac 358 199 74 PRTConus miles 199 Met Lys Leu Thr Cys Val Val Ile Ile Ala Met Leu Phe LeuThr Ala 1 5 10 15 Tyr Gln Leu Ala Thr Ala Ala Ser Tyr Ala Lys Gly LysGln Lys His 20 25 30 Arg Ala Leu Arg Pro Ala Asp Lys His Leu Arg Leu ThrLys Arg Cys 35 40 45 Asn Asp Arg Gly Gly Gly Cys Ser Gln His Pro His CysCys Gly Gly 50 55 60 Thr Cys Asn Lys Leu Ile Gly Val Cys Leu 65 70 20027 PRT Conus arenatus PEPTIDE (1)..(27) Xaa at residue 12 is Pro or Hyp200 Cys Asn Asp Arg Gly Gly Gly Cys Ser Gln His Xaa His Cys Cys Gly 1 510 15 Gly Thr Cys Asn Lys Leu Ile Gly Val Cys Leu 20 25 201 292 DNAConus monachus 201 accaaaacca tcatcaaaat gaaactgacg agtgtggtgatcgtcgccgt gctgctcctg 60 acggcctgtc aactcatcac agctgatgac tccagaggtacgcagaagca tcgtgccctg 120 aggtcggaca ccaaactctc catatcgact cgctgcaagtctacaggaaa atcatgcagt 180 aggattgcgt ataactgctg caccggttct tgcagatcaggtaaatgtgg ctgatccagc 240 gcctgatctt cccccttctg tgctctatcc ttttctgcctgagtcctcct ta 292 202 71 PRT Conus monachus 202 Met Lys Leu Thr Ser ValVal Ile Val Ala Val Leu Leu Leu Thr Ala 1 5 10 15 Cys Gln Leu Ile ThrAla Asp Asp Ser Arg Gly Thr Gln Lys His Arg 20 25 30 Ala Leu Arg Ser AspThr Lys Leu Ser Ile Ser Thr Arg Cys Lys Ser 35 40 45 Thr Gly Lys Ser CysSer Arg Ile Ala Tyr Asn Cys Cys Thr Gly Ser 50 55 60 Cys Arg Ser Gly LysCys Gly 65 70 203 25 PRT Conus monachus PEPTIDE (1)..(25) Xaa at residue13 is Tyr, 125I-Tyr, mono-iodo- Tyr, di-iodo-Tyr, O-sulpho-Tyr orO-phospho-Tyr 203 Cys Lys Ser Thr Gly Lys Ser Cys Ser Arg Ile Ala XaaAsn Cys Cys 1 5 10 15 Thr Gly Ser Cys Arg Ser Gly Lys Cys 20 25 204 258DNA Conus monachus 204 accaaaacca tcatcaaaat gaaactgacg agtgtggtgatcgtcgccgt gctgctcctg 60 acggcctgtc aactcatcac agctgatgac tccagaggtacgcagaagca tcgtgccctg 120 aggtcggaca ccaacctctc catgtcgact cgctgcaagggtaaaggatc ttcatgtagt 180 aggaccatgt ataactgctg caccggttct tgcaacagaggtaaatgtgg ctgatccagc 240 gcctgatctt cccccttc 258 205 71 PRT Conusmonachus 205 Met Lys Leu Thr Ser Val Val Ile Val Ala Val Leu Leu Leu ThrAla 1 5 10 15 Cys Gln Leu Ile Thr Ala Asp Asp Ser Arg Gly Thr Gln LysHis Arg 20 25 30 Ala Leu Arg Ser Asp Thr Asn Leu Ser Met Ser Thr Arg CysLys Gly 35 40 45 Lys Gly Ser Ser Cys Ser Arg Thr Met Tyr Asn Cys Cys ThrGly Ser 50 55 60 Cys Asn Arg Gly Lys Cys Gly 65 70 206 25 PRT Conusmonachus PEPTIDE (1)..(25) Xaa at residue 13 is Tyr, 125I-Tyr,mono-iodo- Tyr, di-iodo-Tyr, O-sulpho-Tyr or O-phospho-Tyr 206 Cys LysGly Lys Gly Ser Ser Cys Ser Arg Thr Met Xaa Asn Cys Cys 1 5 10 15 ThrGly Ser Cys Asn Arg Gly Lys Cys 20 25 207 258 DNA Conus obscurus 207ctctctctct ctctgctgga caggtcgcct ccctgcatga aaggcggatc gtcatgccgc 60ggtactacgg gagtctgttg cggtttttgc agtgatttcg gctataaatg tagggactat 120ccccaaaact gatcttcccc cttctgtgct ctatcctttt ctgtccgagt cctcctgacc 180tgagagtggt catgaaccac tcatcaccta cccctctggg gcttcacagg atctacattg 240aaataaaagc cgcattgc 258 208 39 PRT Conus obscurus 208 Leu Leu Asp ArgSer Pro Pro Cys Met Lys Gly Gly Ser Ser Cys Arg 1 5 10 15 Gly Thr ThrGly Val Cys Cys Gly Phe Cys Ser Asp Phe Gly Tyr Lys 20 25 30 Cys Arg AspTyr Pro Gln Asn 35 209 35 PRT Conus obscurus PEPTIDE (1)..(35) Xaa atresidue 2, 3 and 33 is Pro or Hyp; Xaa at residue 27 and 32 is Tyr,125I-Tyr, mono-iodo-Tyr, di-iodo- Tyr, O-sulpho-Tyr or O-phospho-Tyr 209Ser Xaa Xaa Cys Met Lys Gly Gly Ser Ser Cys Arg Gly Thr Thr Gly 1 5 1015 Val Cys Cys Gly Phe Cys Ser Asp Phe Gly Xaa Lys Cys Arg Asp Xaa 20 2530 Xaa Gln Asn 35 210 259 DNA Conus obscurus 210 ctctctctct ctctgctggacaggtcgact cgctgcttgc ctgacggaac gtcttgcctt 60 tttagtagga tcagatgctgcggtacttgc agttcaatct taaagtcatg tgtgagctga 120 tccagcggtt gatcttcctccctctgtgct ccatcctttt ctgcctgagt tctccttacc 180 tgagagtggt catgaaccactcatcaccta ctcttctgga ggcttcagag gagctacatt 240 gaaataaaag ccgcattgc 259211 32 PRT Conus obscurus 211 Arg Ser Thr Arg Cys Leu Pro Asp Gly ThrSer Cys Leu Phe Ser Arg 1 5 10 15 Ile Arg Cys Cys Gly Thr Cys Ser SerIle Leu Lys Ser Cys Val Ser 20 25 30 212 28 PRT Conus monachus PEPTIDE(1)..(28) Xaa at residue 3 is Pro or Hyp 212 Cys Leu Xaa Asp Gly Thr SerCys Leu Phe Ser Arg Ile Arg Cys Cys 1 5 10 15 Gly Thr Cys Ser Ser IleLeu Lys Ser Cys Val Ser 20 25 213 330 DNA Conus pulicarius misc_feature(1)..(330) n may be any nucleotide 213 atgaaactga cgtgtgtggt gatcatcgccgtgctgttcc tgacggcctg tcaactcatt 60 acagctgaga cttactccag aggtaagcagaagcaccgtg ctttgaggtc aactgacaaa 120 aactccaagt tgactaggca gtgctcgcctaacggtggat cttgttctcg tcattttcac 180 tgctgcagcc tctattgcaa taaaaatactggcgtatgta ttgcaaccta atacccgtgt 240 gtggtcatga accactcaat accctctcctctggaggctt cagaggaact gcattgaaat 300 aaaactgcat tgcnttgacc aaaaaaaaaa330 214 76 PRT Conus pulicarius 214 Met Lys Leu Thr Cys Val Val Ile IleAla Val Leu Phe Leu Thr Ala 1 5 10 15 Cys Gln Leu Ile Thr Ala Glu ThrTyr Ser Arg Gly Lys Gln Lys His 20 25 30 Arg Ala Leu Arg Ser Thr Asp LysAsn Ser Lys Leu Thr Arg Gln Cys 35 40 45 Ser Pro Asn Gly Gly Ser Cys SerArg His Phe His Cys Cys Ser Leu 50 55 60 Tyr Cys Asn Lys Asn Thr Gly ValCys Ile Ala Thr 65 70 75 215 30 PRT Conus pulicarius PEPTIDE (1)..(30)Xaa at residue 1 is Gln or pyro-Glu; Xaa at residue 4 is Pro or Hyp; Xaaat residue 19 is Tyr, 125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyror O-phospho-Tyr 215 Xaa Cys Ser Xaa Asn Gly Gly Ser Cys Ser Arg His PheHis Cys Cys 1 5 10 15 Ser Leu Xaa Cys Asn Lys Asn Thr Gly Val Cys IleAla Thr 20 25 30 216 282 DNA Conus purpurascens 216 atgaaactgacgtgtgtggt gatcgtcgcc gtgctgttcc tgacggcctg tcaactcatc 60 acagctgatgactccagacg tacgcagaag catcgtgccc tgaggtcgac caccaaaggc 120 gccacgtcgaatcgcccctg caagacaccc ggacgaaaat gttttccgca tcagaaggac 180 tgctgcggtcgagcgtgcat catcacaata tgtccctgat cttccccctt ctgtgctgta 240 tccttttctgcctgagtctc cttacctgag agtggtcatg aa 282 217 72 PRT Conus purpurascens217 Met Lys Leu Thr Cys Val Val Ile Val Ala Val Leu Phe Leu Thr Ala 1 510 15 Cys Gln Leu Ile Thr Ala Asp Asp Ser Arg Arg Thr Gln Lys His Arg 2025 30 Ala Leu Arg Ser Thr Thr Lys Gly Ala Thr Ser Asn Arg Pro Cys Lys 3540 45 Thr Pro Gly Arg Lys Cys Phe Pro His Gln Lys Asp Cys Cys Gly Arg 5055 60 Ala Cys Ile Ile Thr Ile Cys Pro 65 70 218 27 PRT Conuspurpurascens PEPTIDE (1)..(27) Xaa at residue 1, 5, 11 and 27 is Pro orHyp 218 Xaa Cys Lys Thr Xaa Gly Arg Lys Cys Phe Xaa His Gln Lys Asp Cys1 5 10 15 Cys Gly Arg Ala Cys Ile Ile Thr Ile Cys Xaa 20 25 219 340 DNAConus purpurascens 219 accaaaacca tcatcaaaat gaaactgacg tgtgtggtgatcgtcgccgt gctgctcctg 60 acggcctgtc aactcatcac agctgatgac tccagaggtacgcagaagca tcgtgccctg 120 aggtcgacca ccaaactctt cacgtcgaaa agctgcaagcttcccggagc atattgtaat 180 gcagaagatt atgactgctg ccttagatgc aaagttggaggtacatgtgg ctgatccagt 240 gcctgatctt cccccttctg tgctctatcc ttttctgcctgagtcctcct tacctaagag 300 tggtcatgaa ccactcatca ccttctcctc tggaggcttc340 220 71 PRT Conus purpurascens 220 Met Lys Leu Thr Cys Val Val IleVal Ala Val Leu Leu Leu Thr Ala 1 5 10 15 Cys Gln Leu Ile Thr Ala AspAsp Ser Arg Gly Thr Gln Lys His Arg 20 25 30 Ala Leu Arg Ser Thr Thr LysLeu Phe Thr Ser Lys Ser Cys Lys Leu 35 40 45 Pro Gly Ala Tyr Cys Asn AlaGlu Asp Tyr Asp Cys Cys Leu Arg Cys 50 55 60 Lys Val Gly Gly Thr Cys Gly65 70 221 26 PRT Conus purpurascens PEPTIDE (1)..(26) Xaa at residue 12is Glu or gamma-carboxy Glu; Xaa at residue 5 is Pro or Hyp; Xaa atresidue 8 and 14 is Tyr, 125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr,O-sulpho-Tyr or O-phospho- Tyr 221 Ser Cys Lys Leu Xaa Gly Ala Xaa CysAsn Ala Xaa Asp Xaa Asp Cys 1 5 10 15 Cys Leu Arg Cys Lys Val Gly GlyThr Cys 20 25 222 317 DNA Conus purpurascens 222 atgaaactga cgtgtgtggtgatcgtcgcc gtgctgttcc tgacggcctg tcaactcatc 60 acagctgatg actccagacgtacgcagaag catcgtgccc tgaggtcgac caccaaacgc 120 gccacgtcga atcgcccctgcaagaaaacc ggacgaaaat gttttccgca tcagaaggac 180 tgctgcggtc gagcgtgcatcatcacaata tgtccctgat cttccccctt ctgtgctgta 240 tccttttctg cctgagtcctccttacctga gagtggtcat gaaccactca tcaccttctc 300 ctctggaggc ttcagag 317223 72 PRT Conus purpurascens 223 Met Lys Leu Thr Cys Val Val Ile ValAla Val Leu Phe Leu Thr Ala 1 5 10 15 Cys Gln Leu Ile Thr Ala Asp AspSer Arg Arg Thr Gln Lys His Arg 20 25 30 Ala Leu Arg Ser Thr Thr Lys ArgAla Thr Ser Asn Arg Pro Cys Lys 35 40 45 Lys Thr Gly Arg Lys Cys Phe ProHis Gln Lys Asp Cys Cys Gly Arg 50 55 60 Ala Cys Ile Ile Thr Ile Cys Pro65 70 224 27 PRT Conus purpurascens PEPTIDE (1)..(27) Xaa at residue 1,11 and 27 is Pro or Hyp 224 Xaa Cys Lys Lys Thr Gly Arg Lys Cys Phe XaaHis Gln Lys Asp Cys 1 5 10 15 Cys Gly Arg Ala Cys Ile Ile Thr Ile CysXaa 20 25 225 328 DNA Conus radiatus 225 gctgatgcct gatcttcatcgttcttccct gtctcctttg gcatcaccaa aaccatcatc 60 aaaatgaaac tgacgtgtgtggtgatcgtc gccgtgctgg tcctgacggc ctgtcaactc 120 atcacagctg atgactccagaggtatgcag aaacatcatg ccctggggtc gatcagcagt 180 ctctttaagt cgacccgtcatggctgcaaa cccctcaaac gtcgttgttt caatgataaa 240 gaatgctgca gcaaattttgcaattcagtc cgaaagcagt gtggataaat ggctaaaaaa 300 ctgaataaaa gccgcattgcaaaaaaaa 328 226 74 PRT Conus radiatus 226 Met Lys Leu Thr Cys Val ValIle Val Ala Val Leu Val Leu Thr Ala 1 5 10 15 Cys Gln Leu Ile Thr AlaAsp Asp Ser Arg Gly Met Gln Lys His His 20 25 30 Ala Leu Gly Ser Ile SerSer Leu Phe Lys Ser Thr Arg His Gly Cys 35 40 45 Lys Pro Leu Lys Arg ArgCys Phe Asn Asp Lys Glu Cys Cys Ser Lys 50 55 60 Phe Cys Asn Ser Val ArgLys Gln Cys Gly 65 70 227 28 PRT Conus radiatus PEPTIDE (1)..(28) Xaa atresidue 15 is Glu or gamma-carboxy Glu; Xaa at residue 5 is Pro or Hyp227 His Gly Cys Lys Xaa Leu Lys Arg Arg Cys Phe Asn Asp Lys Xaa Cys 1 510 15 Cys Ser Lys Phe Cys Asn Ser Val Arg Lys Gln Cys 20 25 228 250 DNAConus radiatus 228 gaaatgaaac tgacgtgtgt ggtgatcgtc gccgtgctggtcctgacggc ctgtcaactc 60 atcacagctg atgactccag aggtatgcag aaacatcatgccctggggtc gatcagcagt 120 ctctttaagt cgacccgtcg tggctgcaaa cccctcaaacgtcgttgttt caatgataaa 180 gaatgctgca gcaaattttg caattcagtc cgaaaccagtgtggataaat ggctaaaaac 240 tgaataaaag 250 229 74 PRT Conus radiatus 229Met Lys Leu Thr Cys Val Val Ile Val Ala Val Leu Val Leu Thr Ala 1 5 1015 Cys Gln Leu Ile Thr Ala Asp Asp Ser Arg Gly Met Gln Lys His His 20 2530 Ala Leu Gly Ser Ile Ser Ser Leu Phe Lys Ser Thr Arg Arg Gly Cys 35 4045 Lys Pro Leu Lys Arg Arg Cys Phe Asn Asp Lys Glu Cys Cys Ser Lys 50 5560 Phe Cys Asn Ser Val Arg Asn Gln Cys Gly 65 70 230 28 PRT Conusradiatus PEPTIDE (1)..(28) Xaa at residue 15 is Glu or gamma-carboxyGlu; Xaa at residue 5 is Pro or Hyp 230 Arg Gly Cys Lys Xaa Leu Lys ArgArg Cys Phe Asn Asp Lys Xaa Cys 1 5 10 15 Cys Ser Lys Phe Cys Asn SerVal Arg Asn Gln Cys 20 25 231 435 DNA Conus radiatus 231 ggaattccgcttgcacggcg aacctgactt catctttctt ccctgcctcc tttggcatca 60 ccaaaaccatcatcaaaatg aaactgacgt gtgtggtgat cgtcgccgtg ctggtcctga 120 cggcctgtcaactcatcaca gctgatgact ccagaggtat gcagaagcat catgccctga 180 ggtcgatcaccaaactctcc ctgtcgactc gctgcaaacc tcccggatca ccatgtagag 240 tttcttcgtataactgctgc tcttcttgca aatcatacaa caagaaatgt ggctgaactt 300 ccccttctgtgctctatcct tttcctgccc gagtcctcca tacctgagag tagtcatgaa 360 ccactgattacctactcctc tggagggcct cagaggagct actttgaaat aaaagcccgc 420 attgcaaaaaaaaaa 435 232 72 PRT Conus radiatus 232 Met Lys Leu Thr Cys Val Val IleVal Ala Val Leu Val Leu Thr Ala 1 5 10 15 Cys Gln Leu Ile Thr Ala AspAsp Ser Arg Gly Met Gln Lys His His 20 25 30 Ala Leu Arg Ser Ile Thr LysLeu Ser Leu Ser Thr Arg Cys Lys Pro 35 40 45 Pro Gly Ser Pro Cys Arg ValSer Ser Tyr Asn Cys Cys Ser Ser Cys 50 55 60 Lys Ser Tyr Asn Lys Lys CysGly 65 70 233 27 PRT Conus radiatus PEPTIDE (1)..(27) Xaa at residue 3,4 and 7 is Pro or Hyp; Xaa at residue 13 and 22 is Tyr, 125I-Tyr,mono-iodo-Tyr, di-iodo- Tyr, O-sulpho-Tyr or O-phospho-Tyr 233 Cys LysXaa Xaa Gly Ser Xaa Cys Arg Val Ser Ser Xaa Asn Cys Cys 1 5 10 15 SerSer Cys Lys Ser Xaa Asn Lys Lys Cys Gly 20 25 234 392 DNA Conus rattus234 ggatccatga aactgacgtg catggtgatc atcgccgtgc tgttcctgac agcctgtcaa 60ttcgatacag ctgcgagcta cgacaaaggt aagcagaaac ctcctactct gaggccagct 120gacaaacaca tcaggttgac caagcgttgc aatgctcgca atgatggttg cagtcaacat 180tctcaatgct gcagtggatc ttgcaataag actgcaggcg tatgtctgta aagctggtct 240gccgtctgat attccctttc tgtgctttat cctcttttgc ctgagtcatc catacctgtg 300aatggttaag agccactcaa tacctactcc tctgggggct tcagaggaac tacattaaat 360aaagccacat tgcaaaaaaa aaaaaaaaaa aa 392 235 74 PRT Conus rattus 235 MetLys Leu Thr Cys Met Val Ile Ile Ala Val Leu Phe Leu Thr Ala 1 5 10 15Cys Gln Phe Asp Thr Ala Ala Ser Tyr Asp Lys Gly Lys Gln Lys Pro 20 25 30Pro Thr Leu Arg Pro Ala Asp Lys His Ile Arg Leu Thr Lys Arg Cys 35 40 45Asn Ala Arg Asn Asp Gly Cys Ser Gln His Ser Gln Cys Cys Ser Gly 50 55 60Ser Cys Asn Lys Thr Ala Gly Val Cys Leu 65 70 236 27 PRT Conus rattus236 Cys Asn Ala Arg Asn Asp Gly Cys Ser Gln His Ser Gln Cys Cys Ser 1 510 15 Gly Ser Cys Asn Lys Thr Ala Gly Val Cys Leu 20 25 237 395 DNAConus rattus 237 ggatccatga aactgacgtg cgtggtgatc atcgccgtgc tgttcctgacagcctgtcaa 60 ctcgatgcag ctgcgagcta cgacaaaggt aagcagaaac ctcctactctgaggccagct 120 gacaaacact tcaggttgat caagcgttgc aatgctcgca atagtggttgcagtcaacat 180 cctcaatgct gcagtggatc ttgcaataag actgcaggcg tatgtctgtaaagctggtct 240 gccgtctgat attccctttc tgtgctttat cctcttttgc ctgagtcatccatacctgtg 300 aatggttaag agccactcaa tacctactcc tctgggggct tcagaggaactacattaaat 360 aaagccacat tgcaacgaaa aaaaaaaaaa aaaaa 395 238 74 PRTConus rattus 238 Met Lys Leu Thr Cys Val Val Ile Ile Ala Val Leu Phe LeuThr Ala 1 5 10 15 Cys Gln Leu Asp Ala Ala Ala Ser Tyr Asp Lys Gly LysGln Lys Pro 20 25 30 Pro Thr Leu Arg Pro Ala Asp Lys His Phe Arg Leu IleLys Arg Cys 35 40 45 Asn Ala Arg Asn Ser Gly Cys Ser Gln His Pro Gln CysCys Ser Gly 50 55 60 Ser Cys Asn Lys Thr Ala Gly Val Cys Leu 65 70 23927 PRT Conus rattus PEPTIDE (1)..(27) Xaa at residue 12 is Pro or Hyp239 Cys Asn Ala Arg Asn Ser Gly Cys Ser Gln His Xaa Gln Cys Cys Ser 1 510 15 Gly Ser Cys Asn Lys Thr Ala Gly Val Cys Leu 20 25 240 390 DNAConus rattus 240 ggatccatga aactgacgtg tgtggtgatc atcgccgtgc tgttcctgacagcctgtcaa 60 ttcgatacag ctgcgagcta cgacaaaggt aagcagaaac ctcctactctgaggccagct 120 gacaaacact tcaggttgat caagcgttgc aatgctcgca atagtggttgcagtcaacat 180 cctcaatgct gcagtggatc ttgcaataag actttgggcg tatgtctgtaaagctggtct 240 gccgtctgat attccctttc tgtgctttat cctcttttgc ctgagtcatccatacctgtg 300 aatggttaag agccactcaa tacctactcc tctgggggct tcagaggaactacattaaat 360 aaagccacat tgaaaaaaaa aaaaaaaaaa 390 241 74 PRT Conusrattus 241 Met Lys Leu Thr Cys Val Val Ile Ile Ala Val Leu Phe Leu ThrAla 1 5 10 15 Cys Gln Phe Asp Thr Ala Ala Ser Tyr Asp Lys Gly Lys GlnLys Pro 20 25 30 Pro Thr Leu Arg Pro Ala Asp Lys His Phe Arg Leu Ile LysArg Cys 35 40 45 Asn Ala Arg Asn Ser Gly Cys Ser Gln His Pro Gln Cys CysSer Gly 50 55 60 Ser Cys Asn Lys Thr Leu Gly Val Cys Leu 65 70 242 27PRT Conus rattus PEPTIDE (1)..(27) Xaa at residue 12 is Pro or Hyp 242Cys Asn Ala Arg Asn Ser Gly Cys Ser Gln His Xaa Gln Cys Cys Ser 1 5 1015 Gly Ser Cys Asn Lys Thr Leu Gly Val Cys Leu 20 25 243 379 DNA Conusstercusmuscarum 243 accaaaacca tcatcaaaat gaaactgacg tgtgtggtgatcgtcgccgt gctgctcctg 60 acggcctgtc aactcatcac agctgatgac tccagaggtacgcagaagca tcgtgccctg 120 aggtcgaaga ccaaactctc catgtcgact cgctgcaagagtaaaggagc aaaatgttca 180 aggcttatgt atgactgctg cagcggttct tgcagcggctacacaggtag atgtggctga 240 tccagcgcct gatcttcccc cttctgtgct ctatccttttctgcctgggt cctccttacc 300 tgagagtggt catgaaccac tcatcaccta ctcctctggaggcctcagag gagttacaat 360 gaaataaaag ccgcattgc 379 244 73 PRT Conusstercusmuscarum 244 Met Lys Leu Thr Cys Val Val Ile Val Ala Val Leu LeuLeu Thr Ala 1 5 10 15 Cys Gln Leu Ile Thr Ala Asp Asp Ser Arg Gly ThrGln Lys His Arg 20 25 30 Ala Leu Arg Ser Lys Thr Lys Leu Ser Met Ser ThrArg Cys Lys Ser 35 40 45 Lys Gly Ala Lys Cys Ser Arg Leu Met Tyr Asp CysCys Ser Gly Ser 50 55 60 Cys Ser Gly Tyr Thr Gly Arg Cys Gly 65 70 24527 PRT Conus stercusmuscarum PEPTIDE (1)..(27) Xaa at residue 13 and 23is Tyr, 125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr orO-phospho-Tyr 245 Cys Lys Ser Lys Gly Ala Lys Cys Ser Arg Leu Met XaaAsp Cys Cys 1 5 10 15 Ser Gly Ser Cys Ser Gly Xaa Thr Gly Arg Cys 20 25246 35 PRT Conus stercusmuscarum PEPTIDE (1)..(35) Xaa at residue 33 isPro or Hyp; Xaa at residue 10, 21, 24 and 32 is Tyr, 125I-Tyr,mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr or O-phospho-Tyr 246 Thr ThrSer Cys Met Gln Ala Gly Ser Xaa Cys Gly Ser Thr Thr Arg 1 5 10 15 IleCys Cys Gly Xaa Cys Ala Xaa Phe Gly Lys Lys Cys Ile Asp Xaa 20 25 30 XaaSer Asn 35 247 380 DNA Conus stercusmuscarum 247 accaaaacca tcatcaaaatgaaactgacg tgtgtggtga tcgtcgccgt gctgctcctg 60 acgacctgtc aactcatcacagctgatgac tccagaggta cgcaggagca tcgtgccctg 120 aggtcgaaga ccaaactctccatgttaact ttgcgctgcg catcttacgg aaaaccttgt 180 ggtattgaca acgactgctgcaatgcatgc gatccagcca gaaatatatg tacgtagctg 240 atccggcgtc tgatcttcccccttctgtgc tctatccttt tctgcctgag tcctccttac 300 ctgagagtgg tcatgaaccactcatcatct actctcctgg aggcctcaga ggagctacaa 360 tgaaataaaa gccgcattgc380 248 72 PRT Conus stercusmuscarum 248 Met Lys Leu Thr Cys Val Val IleVal Ala Val Leu Leu Leu Thr Thr 1 5 10 15 Cys Gln Leu Ile Thr Ala AspAsp Ser Arg Gly Thr Gln Glu His Arg 20 25 30 Ala Leu Arg Ser Lys Thr LysLeu Ser Met Leu Thr Leu Arg Cys Ala 35 40 45 Ser Tyr Gly Lys Pro Cys GlyIle Asp Asn Asp Cys Cys Asn Ala Cys 50 55 60 Asp Pro Ala Arg Asn Ile CysThr 65 70 249 26 PRT Conus stercusmuscarum PEPTIDE (1)..(26) Xaa atresidue 7 and 20 is Pro or Hyp; Xaa at residue4 is Tyr, 125I-Tyr,mono-iodo-Tyr, di-iodo- Tyr, O-sulpho-Tyr or O-phospho-Tyr 249 Cys AlaSer Xaa Gly Lys Xaa Cys Gly Ile Asp Asn Asp Cys Cys Asn 1 5 10 15 AlaCys Asp Xaa Ala Arg Asn Ile Cys Thr 20 25 250 388 DNA Conusstercusmuscarum 250 ggatccatga aactgacgtg tgtggtgatt gtcgccgtgctgctcctgac ggcctgtcaa 60 ctcatcacag ctgatgactc cagaggtacg caggagcatcgtgccctgag gtcgaagacc 120 aaactctcca tgttaacttt gcgctgcgta tcttacggaaaaccttgtgg tattgacaac 180 gactgctgca atgcatgcga tccagccaga aatatatgtacgtagctgat ccggcgtctg 240 atcttccccc ttctgtgctc tatccttttc tgcctgggtcctccttacct gagagtggtc 300 atgaaccact catcacctac tcctctggag gcctcagaggagttacaatg aaataaaagc 360 cgcattgcaa aaaaaaaaaa aaaaaaaa 388 251 72 PRTConus stercusmuscarum 251 Met Lys Leu Thr Cys Val Val Ile Val Ala ValLeu Leu Leu Thr Ala 1 5 10 15 Cys Gln Leu Ile Thr Ala Asp Asp Ser ArgGly Thr Gln Glu His Arg 20 25 30 Ala Leu Arg Ser Lys Thr Lys Leu Ser MetLeu Thr Leu Arg Cys Val 35 40 45 Ser Tyr Gly Lys Pro Cys Gly Ile Asp AsnAsp Cys Cys Asn Ala Cys 50 55 60 Asp Pro Ala Arg Asn Ile Cys Thr 65 70252 26 PRT Conus stercusmuscarum PEPTIDE (1)..(26) Xaa at residue 7 and20 is Pro or Hyp; Xaa at residue 4 is Tyr, 125I-Tyr, mono-iodo-Tyr,di-iodo- Tyr, O-sulpho-Tyr or O-phospho-Tyr 252 Cys Val Ser Xaa Gly LysXaa Cys Gly Ile Asp Asn Asp Cys Cys Asn 1 5 10 15 Ala Cys Asp Xaa AlaArg Asn Ile Cys Thr 20 25 253 264 DNA Conus striatus 253 accaaaaccatcatcaaaat gaaactgacg tgtgtggtga tcgtcgccgt gctgctcctg 60 acggcctgtcaactcatcac agctgatgac tccagaggta cgcagaagca tcgttccctg 120 aggtcgaccaccaaagtctc caaggcgact gactgcattg aagccggaaa ttattgcgga 180 cctactgttatgaaaatctg ctgcggcttt tgcagtccat acagcaaaat atgtatgaac 240 tatcccaaaaattgatcttc cccc 264 254 78 PRT Conus striatus 254 Met Lys Leu Thr CysVal Val Ile Val Ala Val Leu Leu Leu Thr Ala 1 5 10 15 Cys Gln Leu IleThr Ala Asp Asp Ser Arg Gly Thr Gln Lys His Arg 20 25 30 Ser Leu Arg SerThr Thr Lys Val Ser Lys Ala Thr Asp Cys Ile Glu 35 40 45 Ala Gly Asn TyrCys Gly Pro Thr Val Met Lys Ile Cys Cys Gly Phe 50 55 60 Cys Ser Pro TyrSer Lys Ile Cys Met Asn Tyr Pro Lys Asn 65 70 75 255 36 PRT Conusstriatus PEPTIDE (1)..(36) Xaa at residue 6 is Glu or gamma-carboxy Glu;Xaa at residue 13,25 and 34 is Pro or Hyp; Xaa at residue 10, 26 and 33is Tyr, 125 I-Tyr, mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr orO-phospho-Tyr 255 Ala Thr Asp Cys Ile Xaa Ala Gly Asn Xaa Cys Gly XaaThr Val Met 1 5 10 15 Lys Ile Cys Cys Gly Phe Cys Ser Xaa Xaa Ser LysIle Cys Met Asn 20 25 30 Xaa Xaa Lys Asn 35 256 233 DNA Conus striatus256 gtcgactcgc tgcaagctta aaggacaatc atgtcgtagg actatgtatg actgctgcag 60cggttcttgc ggcaggagag gtaaatgtgg ctgatccagc gcctgatctc cccccttctg 120tgctctatcc ttttctgcct gggtcctcct tacctgagag tggtcatgaa ccactcatca 180cctactcctc tggaggcctc agaggagcta caatgaaata aaagccgcat tgc 233 257 30PRT Conus striatus 257 Ser Thr Arg Cys Lys Leu Lys Gly Gln Ser Cys ArgArg Thr Met Tyr 1 5 10 15 Asp Cys Cys Ser Gly Ser Cys Gly Arg Arg GlyLys Cys Gly 20 25 30 258 26 PRT Conus striatus PEPTIDE (1)..(26) Xaa atresidue 13 is Tyr, 125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr orO-phospho-Tyr 258 Cys Lys Leu Lys Gly Gln Ser Cys Arg Arg Thr Met XaaAsp Cys Cys 1 5 10 15 Ser Gly Ser Cys Gly Arg Arg Gly Lys Cys 20 25 259310 DNA Conus striatus 259 accaaaacca tcatcaaaat gaaactgacg tgtgtggtgatcgtcgccgt gctgctcctg 60 acggcctgtc aactcatcac agctgatgac tccagaggtacgcagaagca tcgtgccctg 120 aggtcggaca ccaaactctc catgtcgact cgctgcaaggctgcaggaaa atcatgcagt 180 aggattgcgt ataactgctg caccggttct tgcagatcaggtaaatgcgg ctgatccagc 240 gcctgatctt cccccttctg tgctctatcc tttctgcctgagtcctctta cctgagagtg 300 gtcatgaacc 310 260 71 PRT Conus striatus 260Met Lys Leu Thr Cys Val Val Ile Val Ala Val Leu Leu Leu Thr Ala 1 5 1015 Cys Gln Leu Ile Thr Ala Asp Asp Ser Arg Gly Thr Gln Lys His Arg 20 2530 Ala Leu Arg Ser Asp Thr Lys Leu Ser Met Ser Thr Arg Cys Lys Ala 35 4045 Ala Gly Lys Ser Cys Ser Arg Ile Ala Tyr Asn Cys Cys Thr Gly Ser 50 5560 Cys Arg Ser Gly Lys Cys Gly 65 70 261 25 PRT Conus striatus PEPTIDE(1)..(25) Xaa at residue 13 is Tyr, 125I-Tyr, mono-iodo-Tyr,di-iodo-Tyr, O-sulpho-Tyr or O-phospho-Tyr 261 Cys Lys Ala Ala Gly LysSer Cys Ser Arg Ile Ala Xaa Asn Cys Cys 1 5 10 15 Thr Gly Ser Cys ArgSer Gly Lys Cys 20 25 262 256 DNA Conus striatus 262 accaaaaccatcatcaaaat gaaactgacg tgtgtggtga tcgtcgccgt gctgctcctg 60 acggcctgtcaactcatcac agctgatgac tccagaggta cgcaggagca tcgtgccctg 120 aggtcggacaccaaactctc catgttaact ttgcgctgcg aatcttacgg aaaaccttgt 180 ggtatttacaacgactgctg caatgcatgc gatccagcca aaaagacatg tacgtagctg 240 atccggcgtctgatct 256 263 72 PRT Conus striatus 263 Met Lys Leu Thr Cys Val Val IleVal Ala Val Leu Leu Leu Thr Ala 1 5 10 15 Cys Gln Leu Ile Thr Ala AspAsp Ser Arg Gly Thr Gln Glu His Arg 20 25 30 Ala Leu Arg Ser Asp Thr LysLeu Ser Met Leu Thr Leu Arg Cys Glu 35 40 45 Ser Tyr Gly Lys Pro Cys GlyIle Tyr Asn Asp Cys Cys Asn Ala Cys 50 55 60 Asp Pro Ala Lys Lys Thr CysThr 65 70 264 26 PRT Conus striatus PEPTIDE (1)..(26) Xaa at residue 2is Glu or gamma-carboxy Glu; Xaa at residue 7 and 20 is Pro or Hyp; Xaaat residue 4 and 11 is Tyr, 125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr,O-sulpho-Tyr or O-phospho-Tyr 264 Cys Xaa Ser Xaa Gly Lys Xaa Cys GlyIle Xaa Asn Asp Cys Cys Asn 1 5 10 15 Ala Cys Asp Xaa Ala Lys Lys ThrCys Thr 20 25 265 229 DNA Conus striatus 265 tctaggtcct ccggcagcccctgtggtgtt actagtatat gctgtggtag atgctatagg 60 ggtaaatgta cgtagctcatcgggcgtctg atcttccccc ttctgtgctc catccttttc 120 tgcctgagtc ctccttacctgagagtggtc gtgaaccact catcgcctac tcctctggag 180 gcttcagagg ggctacactaaaataaaagc tatattgcaa tgaaaaaaa 229 266 24 PRT Conus striatus 266 CysArg Ser Ser Gly Ser Pro Cys Gly Val Thr Ser Ile Cys Cys Gly 1 5 10 15Arg Cys Tyr Arg Gly Lys Cys Thr 20 267 24 PRT Conus striatus PEPTIDE(1)..(24) Xaa at residue 7 is Pro or Hyp; Xaa at residue 19 is Tyr,125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr or O-phospho-Tyr 267Cys Arg Ser Ser Gly Ser Xaa Cys Gly Val Thr Ser Ile Cys Cys Gly 1 5 1015 Arg Cys Xaa Arg Gly Lys Cys Thr 20 268 26 PRT Conus striatus PEPTIDE(1)..(26) Xaa at residue 13 is Tyr, 125I-Tyr, mono- iodo-Tyr,di-iodo-Tyr, O-sulpho-Tyr or O-phospho-Tyr 268 Cys Lys Leu Lys Gly GlnSer Cys Arg Lys Thr Ser Xaa Asp Cys Cys 1 5 10 15 Ser Gly Ser Cys GlyArg Ser Gly Lys Cys 20 25 269 292 DNA Conus striolatus 269 accaaaaccatcatcaaaat gaaactgacg tgtgtggtga tcgtcgtctt gctgctcctg 60 acgacctgtcgtctcatcac agctgatgac tccagaggta cgcagaagca tcgttccctg 120 aggtcgactactaaagtctc catgtcgact cgctgcaagg gtaaaggagc atcatgtctt 180 aggactgcgtatgactgctg caccggttct tgcaacagag gtagatgtgg ctgatccagc 240 gtctgatcttcccccttctg tgctctatcc ttttctgctt gagtcctcct ta 292 270 71 PRT Conusstriolatus 270 Met Lys Leu Thr Cys Val Val Ile Val Val Leu Leu Leu LeuThr Thr 1 5 10 15 Cys Arg Leu Ile Thr Ala Asp Asp Ser Arg Gly Thr GlnLys His Arg 20 25 30 Ser Leu Arg Ser Thr Thr Lys Val Ser Met Ser Thr ArgCys Lys Gly 35 40 45 Lys Gly Ala Ser Cys Leu Arg Thr Ala Tyr Asp Cys CysThr Gly Ser 50 55 60 Cys Asn Arg Gly Arg Cys Gly 65 70 271 25 PRT Conusstriolatus PEPTIDE (1)..(25) Xaa at residue 13 is Tyr, 125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr or O-phospho-Tyr 271 Cys Lys Gly LysGly Ala Ser Cys Leu Arg Thr Ala Xaa Asp Cys Cys 1 5 10 15 Thr Gly SerCys Asn Arg Gly Arg Cys 20 25 272 259 DNA Conus striolatus 272accaaaacca tcatcaaaat gaaactgacg tgtgtggtga tcgtcgccgt tctgctgacg 60gcgtgtcaac tcatcacagc tgaggactcc agaggtacac agaagcatcg taccctgagg 120tcgaccgtca gacgctccaa gtccgagttg actacgagat gcaggccttc aggatccaac 180tgtggtaata ttagtatctg ctgtggtaga tgcgttaaca gaagatgtac gtagctcatc 240gggcgtctga tctttcccc 259 273 71 PRT Conus striolatus 273 Met Lys Leu ThrCys Val Val Ile Val Ala Val Leu Leu Thr Ala Cys 1 5 10 15 Gln Leu IleThr Ala Glu Asp Ser Arg Gly Thr Gln Lys His Arg Thr 20 25 30 Leu Arg SerThr Val Arg Arg Ser Lys Ser Glu Leu Thr Thr Arg Cys 35 40 45 Arg Pro SerGly Ser Asn Cys Gly Asn Ile Ser Ile Cys Cys Gly Arg 50 55 60 Cys Val AsnArg Arg Cys Thr 65 70 274 24 PRT Conus striolatus PEPTIDE (1)..(24) Xaaat residue 3 is Pro or Hyp 274 Cys Arg Xaa Ser Gly Ser Asn Cys Gly AsnIle Ser Ile Cys Cys Gly 1 5 10 15 Arg Cys Val Asn Arg Arg Cys Thr 20 275280 DNA Conus striolatus 275 accaaaacca tcatcaaaat gaaactgacg tgtgtggtgatcgtcgccgt tctgttcctg 60 acggcgtgtc aactcatcac agctgaggac tccagaggtacacagaagca tcgttccctg 120 aggtcgacta ccaaagtctc caagtcgact agctgcatgaaagccgggtc ttattgcgtc 180 gctactacga gaatctgctg cggttattgc gcttatttcggcaaaatatg tattgactat 240 cccaaaaact gatcttcccc ctactgtgct ctatcctttt280 276 77 PRT Conus striolatus 276 Met Lys Leu Thr Cys Val Val Ile ValAla Val Leu Phe Leu Thr Ala 1 5 10 15 Cys Gln Leu Ile Thr Ala Glu AspSer Arg Gly Thr Gln Lys His Arg 20 25 30 Ser Leu Arg Ser Thr Thr Lys ValSer Lys Ser Thr Ser Cys Met Lys 35 40 45 Ala Gly Ser Tyr Cys Val Ala ThrThr Arg Ile Cys Cys Gly Tyr Cys 50 55 60 Ala Tyr Phe Gly Lys Ile Cys IleAsp Tyr Pro Lys Asn 65 70 75 277 35 PRT Conus striolatus PEPTIDE(1)..(35) Xaa at residue 33 is Pro or Hyp; Xaa at residue 10, 21, 24 and32 is Tyr, 125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr orO-phospho-Tyr 277 Ser Thr Ser Cys Met Lys Ala Gly Ser Xaa Cys Val AlaThr Thr Arg 1 5 10 15 Ile Cys Cys Gly Xaa Cys Ala Xaa Phe Gly Lys IleCys Ile Asp Xaa 20 25 30 Xaa Lys Asn 35 278 174 DNA Conus textile 278gttgactcgg tactgcacgc ctcatggagg acattgtggt tatcataatg actgctgcag 60tcatcaatgc aatataaaca gaaataaatg tgagtagctg atctggcatc tgatctgtgc 120tcgtccttac ctgagagtgg tcatgaacca ctcatcacct actcctctgg aggc 174 279 31PRT Conus textile 279 Leu Thr Arg Tyr Cys Thr Pro His Gly Gly His CysGly Tyr His Asn 1 5 10 15 Asp Cys Cys Ser His Gln Cys Asn Ile Asn ArgAsn Lys Cys Glu 20 25 30 280 28 PRT Conus textile PEPTIDE (1)..(28) Xaaat residue 28 is Glu or gamma-carboxy Glu; Xaa at residue 4 is Pro orHyp; Xaa at residue 1 and 11 is Tyr, 125I-Tyr, mono-iodo-Tyr,di-iodo-Tyr, O-sulpho-Tyr or O-phospho- Tyr 280 Xaa Cys Thr Xaa His GlyGly His Cys Gly Xaa His Asn Asp Cys Cys 1 5 10 15 Ser His Gln Cys AsnIle Asn Arg Asn Lys Cys Xaa 20 25 281 28 PRT Conus textile PEPTIDE(1)..(28) Xaa at residue 28 is Glu or gamma-carboxy Glu; Xaa at residue4 is Pro or Hyp; Xaa at residue 1 and 11 is Tyr, 1 -Tyr, di-iodo-Tyr,O-sulpho-Tyr or O-phospho-Tyr 281 Xaa Cys Thr Xaa Xaa Gly Gly His CysGly Xaa His Asn Asp Cys Cys 1 5 10 15 Ser His Gln Cys Asn Ile Asn ArgAsn Lys Cys Xaa 20 25 282 379 DNA Conus tulipa 282 accaaaacca tcatcaaaatgaaactgacg tgtgtggtga tcgtcgccgt gctgctcctg 60 acggcctgtc agctcatcacagctctgcac tccagaggta cgcagaagca tcgtgccctg 120 gggcggacca ccaaactcaccttgtcgact cgctgcaaat cacccggatc tccatgttca 180 ccgactagtt ataattgctgctggtcttgc agtccataca gaaaaaaatg taggggctaa 240 tccagcgcct gattttcccccttctgtgct ctattccttt ctgcctgagt cctccttacc 300 tgaaagtggt catgaaccactcatcaccta cttctctgga ggcttcggag gagctacatt 360 gaaataaaag ccgcattgc 379283 73 PRT Conus tulipa 283 Met Lys Leu Thr Cys Val Val Ile Val Ala ValLeu Leu Leu Thr Ala 1 5 10 15 Cys Gln Leu Ile Thr Ala Leu His Ser ArgGly Thr Gln Lys His Arg 20 25 30 Ala Leu Gly Arg Thr Thr Lys Leu Thr LeuSer Thr Arg Cys Lys Ser 35 40 45 Pro Gly Ser Pro Cys Ser Pro Thr Ser TyrAsn Cys Cys Trp Ser Cys 50 55 60 Ser Pro Tyr Arg Lys Lys Cys Arg Gly 6570 284 27 PRT Conus tulipa PEPTIDE (1)..(27) Xaa at residue 3, 7, 10 and21 is Pro or Hyp; Xaa at residue 17 is Trp or Bromo Trp; Xaa at residue13 and 22 is Tyr, 125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr orO-phospho-Tyr 284 Cys Lys Ser Xaa Gly Ser Xaa Cys Ser Xaa Thr Ser XaaAsn Cys Cys 1 5 10 15 Xaa Ser Cys Ser Xaa Xaa Arg Lys Lys Cys Arg 20 25285 379 DNA Conus tulipa 285 accaaaacca tcatcaaaat gaaactgacg tgtgtggtgatcgtcgccgt gctgctcctg 60 acggcctgtc agctcatcac agctctgcac tccagaggtacgcagaagca tcgtgccctg 120 gggtcgacca ccaaactcac cttgtcgact cgctgcttgtcacccggatc ttcatgttca 180 ccgactagtt ataattgctg caggtcttgc aatccatacagcagaaaatg taggggctaa 240 tccagcgcct gatcttcccc cttctgtgct ctattcctttctgcctgagt cctccttacc 300 tgaaagtggt catgaaccac tcatcaccta cttctctggaggcttcggag gagctacatt 360 gaaataaaag ccgcattgc 379 286 73 PRT Conustulipa 286 Met Lys Leu Thr Cys Val Val Ile Val Ala Val Leu Leu Leu ThrAla 1 5 10 15 Cys Gln Leu Ile Thr Ala Leu His Ser Arg Gly Thr Gln LysHis Arg 20 25 30 Ala Leu Gly Ser Thr Thr Lys Leu Thr Leu Ser Thr Arg CysLeu Ser 35 40 45 Pro Gly Ser Ser Cys Ser Pro Thr Ser Tyr Asn Cys Cys ArgSer Cys 50 55 60 Asn Pro Tyr Ser Arg Lys Cys Arg Gly 65 70 287 27 PRTConus tulipa PEPTIDE (1)..(27) Xaa at residue 4, 10 and 21 is Pro orHyp; Xaa at residue 13 and 22 is Tyr, 125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr or O-phospho-Tyr 287 Cys Leu Ser Xaa Gly Ser SerCys Ser Xaa Thr Ser Xaa Asn Cys Cys 1 5 10 15 Arg Ser Cys Asn Xaa XaaSer Arg Lys Cys Arg 20 25 288 401 DNA Conus viola 288 accaaaaccatcatcaaaat gaaactgacg tgtgtggtga tcgtcgccgt gctgctcctg 60 acggcctgtcagctcattac agctgatgac tccagaggta cgcagttgca tcgtgccctg 120 aggaaggccaccaaactccc cgtgtcgact cgctgcatta ctttaggaac acgatgtaag 180 gttccgagtcaatgctgcag atcttcttgc aagaacggtc gttgtgctcc atcccctgaa 240 gaatggtaaatgtggctgat ccagcgcctg atcttccccc ttctgactgt ctccgacctt 300 ttctgcctgagtcctcctta cctgagaggt gtcatgaacc actcatcacc tactcccctg 360 gaagcttcagaggagctaca ttgaaataaa agccgcattg c 401 289 76 PRT Conus viola 289 MetLys Leu Thr Cys Val Val Ile Val Ala Val Leu Leu Leu Thr Ala 1 5 10 15Cys Gln Leu Ile Thr Ala Asp Asp Ser Arg Gly Thr Gln Leu His Arg 20 25 30Ala Leu Arg Lys Ala Thr Lys Leu Pro Val Ser Thr Arg Cys Ile Thr 35 40 45Leu Gly Thr Arg Cys Lys Val Pro Ser Gln Cys Cys Arg Ser Ser Cys 50 55 60Lys Asn Gly Arg Cys Ala Pro Ser Pro Glu Glu Trp 65 70 75 290 31 PRTConus viola PEPTIDE (1)..(31) Xaa at residue 29 and 30 is Glu or gamma-carboxy Glu; Xaa at residue 11, 26 and 28 is Pro or Hyp; Xaa at residue31 is Trp or Bromo Trp 290 Cys Ile Thr Leu Gly Thr Arg Cys Lys Val XaaSer Gln Cys Cys Arg 1 5 10 15 Ser Ser Cys Lys Asn Gly Arg Cys Ala XaaSer Xaa Xaa Xaa Xaa 20 25 30 291 372 DNA Conus viola 291 accaaaaccatcatcaaaat gaaactgacg tgtgtggtga tcgtcgccgt gctgctcctg 60 acggcctgtcagctcattat agctggggac tccagaggta cgcagttgca tcgtgccctg 120 aggaaggccaccaaactctc cgtgtcgact cgctgcaaga gtagaggatc atcatgtcgt 180 aggacttcgtatgactgctg cacgggttct tgcagaaatg gtaaatgtgg ctgatccagc 240 gcctgatcttcccccttctg tgctccatcc ttttctgcct gagtcctcct tacctgagag 300 tgggcatgaaccactcatca cctactccct ggaagcttca gaggagctac attgaaataa 360 aagccgcatt gc372 292 71 PRT Conus viola 292 Met Lys Leu Thr Cys Val Val Ile Val AlaVal Leu Leu Leu Thr Ala 1 5 10 15 Cys Gln Leu Ile Ile Ala Gly Asp SerArg Gly Thr Gln Leu His Arg 20 25 30 Ala Leu Arg Lys Ala Thr Lys Leu SerVal Ser Thr Arg Cys Lys Ser 35 40 45 Arg Gly Ser Ser Cys Arg Arg Thr SerTyr Asp Cys Cys Thr Gly Ser 50 55 60 Cys Arg Asn Gly Lys Cys Gly 65 70293 25 PRT Conus viola PEPTIDE (1)..(25) Xaa at residue 13 is Tyr,125I-Tyr, mono- iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr or O-phospho-Tyr 293Cys Lys Ser Arg Gly Ser Ser Cys Arg Arg Thr Ser Xaa Asp Cys Cys 1 5 1015 Thr Gly Ser Cys Arg Asn Gly Lys Cys 20 25 294 380 DNA Conus viola 294accaaaacca tcatcaaaat gaaactgacg tgtgtggcga tcgtcgccgt gctgctcctg 60acggcctgtc agctcattac agctgaagac tccagaggta cgcatgagca tcttgccctg 120aagtcgacct ccaaagtctc caagtcgact agctgcatgg aagccagatc ttattgcgga 180cctgctacta cgaaaatctg ctgcgatttt tgcagtccat tcagcgatag atgtatgaac 240aatcccaaca attgatcttc ccccttgtgt gctccatctt ttctgcctga gtcctcctta 300cctgagagtg gtcatgaacc actcatcacc tactcctctg gaggcttcag aggagttaca 360ttgaaataaa agccgcatgc 380 295 78 PRT Conus viola 295 Met Lys Leu Thr CysVal Ala Ile Val Ala Val Leu Leu Leu Thr Ala 1 5 10 15 Cys Gln Leu IleThr Ala Glu Asp Ser Arg Gly Thr His Glu His Leu 20 25 30 Ala Leu Lys SerThr Ser Lys Val Ser Lys Ser Thr Ser Cys Met Glu 35 40 45 Ala Arg Ser TyrCys Gly Pro Ala Thr Thr Lys Ile Cys Cys Asp Phe 50 55 60 Cys Ser Pro PheSer Asp Arg Cys Met Asn Asn Pro Asn Asn 65 70 75 296 36 PRT Conus violaPEPTIDE (1)..(36) Xaa at residue6 is Glu or gamma-carboxy Glu; Xaa atresidue 13, 25 and 34 is Pro or Hyp; Xaa at residue 10 is Tyr, 125I-Tyr,mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr or O- phospho-Tyr 296 Ser ThrSer Cys Met Xaa Ala Arg Ser Xaa Cys Gly Xaa Ala Thr Thr 1 5 10 15 LysIle Cys Cys Asp Phe Cys Ser Xaa Phe Ser Asp Arg Cys Met Asn 20 25 30 AsnXaa Asn Asn 35 297 373 DNA Conus viola 297 accaaaacca tcatcaaaatgaaactgacg tgtgtggtga tcgtcgccgt gctgctcctg 60 acggcctgtc agctcattacagctgaggac tccagaggta cgcagttgca tcgtgccctg 120 aggaagacca ccaaactctccttgtcgact cgctgcaagg gtccaggagc catatgtata 180 aggattgcgt ataactgctgcaagtattct tgcggaaatg gtaaatgtgg ctgatccagc 240 gcctgatctt cccccttgtgtgctccatcc tttttctgcc tgagtcctcc ttacctgaga 300 gtggtcatga accactcatcacctactcct ctggaggctt cagaggagct acattgaaat 360 aaaagccgca tgc 373 29871 PRT Conus viola 298 Met Lys Leu Thr Cys Val Val Ile Val Ala Val LeuLeu Leu Thr Ala 1 5 10 15 Cys Gln Leu Ile Thr Ala Glu Asp Ser Arg GlyThr Gln Leu His Arg 20 25 30 Ala Leu Arg Lys Thr Thr Lys Leu Ser Leu SerThr Arg Cys Lys Gly 35 40 45 Pro Gly Ala Ile Cys Ile Arg Ile Ala Tyr AsnCys Cys Lys Tyr Ser 50 55 60 Cys Gly Asn Gly Lys Cys Gly 65 70 299 25PRT Conus viola PEPTIDE (1)..(25) Xaa at residue 3 is Pro or Hyp; Xaa atresidue 13 and 18 is Tyr, 125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr,O-sulpho- Tyr or O-phospho-Tyr 299 Cys Lys Gly Xaa Gly Ala Ile Cys IleArg Ile Ala Xaa Asn Cys Cys 1 5 10 15 Lys Xaa Ser Cys Gly Asn Gly LysCys 20 25 300 353 DNA Conus viola 300 accaaaacca tcatcaaaat gaaactgacgtgtgtggtga tcgtcgccgt gctgttcctg 60 acggcctgtc aattcatcac agctgatgactccagaagta cgcagaagca tcgtgccctg 120 aggtcgacca ccaaacactt tatgttgacttggtactgca cgccttatgg aggacattgt 180 ggttattata atgactgctg cagtcatcaatgcaatataa acagaaataa atgtgagtag 240 ctgatccggc atctgatctg tgctcgccctaacctgagag tggtcatgaa ccactcatca 300 tctactcctc tggaggcttc agaggagctacatggaaata aaagccgcat tgc 353 301 73 PRT Conus viola 301 Met Lys Leu ThrCys Val Val Ile Val Ala Val Leu Phe Leu Thr Ala 1 5 10 15 Cys Gln PheIle Thr Ala Asp Asp Ser Arg Ser Thr Gln Lys His Arg 20 25 30 Ala Leu ArgSer Thr Thr Lys His Phe Met Leu Thr Trp Tyr Cys Thr 35 40 45 Pro Tyr GlyGly His Cys Gly Tyr Tyr Asn Asp Cys Cys Ser His Gln 50 55 60 Cys Asn IleAsn Arg Asn Lys Cys Glu 65 70 302 28 PRT Conus viola PEPTIDE (1)..(28)Xaa at residue 28 is Glu or gamma-carboxy Glu; Xaa at residue 4 is Proor Hyp; Xaa at residue 1, 5, 11 and 12 is Tyr, 125I-Tyr, mono-iodo-Tyr,di-iodo-Tyr, O-sulpho-Tyr or O- phospho-Tyr 302 Xaa Cys Thr Xaa Xaa GlyGly His Cys Gly Xaa Xaa Asn Asp Cys Cys 1 5 10 15 Ser His Gln Cys AsnIle Asn Arg Asn Lys Cys Xaa 20 25 303 294 DNA Conus pulicarius 303ggatccatga aactgacgtg cgtggtgatt atcgccgtgc tgttcctgac ggcctgtcaa 60ctcattacag ctgagactta ctccagaggt aagcagatgc accgtgctct gaggtcaact 120gacaaaaact ccaagttgac cagggaatgc acacctccag atggagcttg tggtttacct 180acacactgct gcgggttttg cgatatggca aacaacagat gtctgtaaag cgtctgatat 240tccccttctg tgctctatcc tctttggcct gagtcatcca tacctgtgct cgag 294 304 73PRT Conus pulicarius 304 Met Lys Leu Thr Cys Val Val Ile Ile Ala Val LeuPhe Leu Thr Ala 1 5 10 15 Cys Gln Leu Ile Thr Ala Glu Thr Tyr Ser ArgGly Lys Gln Met His 20 25 30 Arg Ala Leu Arg Ser Thr Asp Lys Asn Ser LysLeu Thr Arg Glu Cys 35 40 45 Thr Pro Pro Asp Gly Ala Cys Gly Leu Pro ThrHis Cys Cys Gly Phe 50 55 60 Cys Asp Met Ala Asn Asn Arg Cys Leu 65 70305 27 PRT Conus pulicarius PEPTIDE (1)..(27) Xaa at residue 1 is Glu orgamma-carboxy Glu; Xaa at residue 4, 5 and 12 is Pro or Hyp 305 Xaa CysThr Xaa Xaa Asp Gly Ala Cys Gly Leu Xaa Thr His Cys Cys 1 5 10 15 GlyPhe Cys Asp Met Ala Asn Asn Arg Cys Leu 20 25 306 294 DNA Conuspulicarius 306 ggatccatga aactgacgtg cgtggtgatt atcgccgtgc tgttcctgacggcctgtcaa 60 ctcattacag ctgagactta ctccagaggt aagcagatgc accgtgctctgaggtcaact 120 gacaaaaact cccagttgac cagggaatgc acacctccag gtggagcttgtggtttacct 180 acacactgct gcgggttttg cgatatggca aacaacagat gtctgtaaagcgtctgatat 240 tccccttctg tgctctatcc tctttggcct gagtcatcca tacctgtgctcgag 294 307 73 PRT Conus pulicarius 307 Met Lys Leu Thr Cys Val Val IleIle Ala Val Leu Phe Leu Thr Ala 1 5 10 15 Cys Gln Leu Ile Thr Ala GluThr Tyr Ser Arg Gly Lys Gln Met His 20 25 30 Arg Ala Leu Arg Ser Thr AspLys Asn Ser Gln Leu Thr Arg Glu Cys 35 40 45 Thr Pro Pro Gly Gly Ala CysGly Leu Pro Thr His Cys Cys Gly Phe 50 55 60 Cys Asp Met Ala Asn Asn ArgCys Leu 65 70 308 27 PRT Conus pulicarius PEPTIDE (1)..(27) Xaa atresidue 1 is Glu or gamma-carboxy Glu; Xaa at residue 4, 5 and 12 is Proor Hyp 308 Xaa Cys Thr Xaa Xaa Gly Gly Ala Cys Gly Leu Xaa Thr His CysCys 1 5 10 15 Gly Phe Cys Asp Met Ala Asn Asn Arg Cys Leu 20 25 309 307DNA Conus rattus 309 ggatccatga aactgacgtg tgtggtgatc atcgccgtgctgttcctggc agcctgtcaa 60 cctgttacaa ctgagacttt ctccagaggt aaggagaagcgtcgtgctct gaggtcaact 120 gacggcaact cccggttgac cagggcatgc acgcctgaaggtggagcctg tagtagtggg 180 cgtcactgct gcggcttttg cgataacgtg tcccacacgtgctatggtga aacaccatct 240 ctccactgat gtttcccctt ctgtgctcta tcttcttttgcctgagtcat ccatacctgt 300 gctcgag 307 310 80 PRT Conus rattus 310 MetLys Leu Thr Cys Val Val Ile Ile Ala Val Leu Phe Leu Ala Ala 1 5 10 15Cys Gln Pro Val Thr Thr Glu Thr Phe Ser Arg Gly Lys Glu Lys Arg 20 25 30Arg Ala Leu Arg Ser Thr Asp Gly Asn Ser Arg Leu Thr Arg Ala Cys 35 40 45Thr Pro Glu Gly Gly Ala Cys Ser Ser Gly Arg His Cys Cys Gly Phe 50 55 60Cys Asp Asn Val Ser His Thr Cys Tyr Gly Glu Thr Pro Ser Leu His 65 70 7580 311 34 PRT Conus rattus PEPTIDE (1)..(34) Xaa at residue 5 and 29 isGlu or gamma- carboxy Glu; Xaa at residue 4 and 31 is Pro or Hyp; Xaa atresidue 27 is Tyr, 125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr orO-phospho-Tyr 311 Ala Cys Thr Xaa Xaa Gly Gly Ala Cys Ser Ser Gly ArgHis Cys Cys 1 5 10 15 Gly Phe Cys Asp Asn Val Ser His Thr Cys Xaa GlyXaa Thr Xaa Ser 20 25 30 Leu His 312 342 DNA Conus stercusmuscarummisc_feature (1)..(342) n may be any nucleotide 312 agatccatgaaactgacgtg cgtggtgatc gtcgccgtgc tgctcctgac ggcctgtcaa 60 ctcatcacagctgatgactc cagaggtacg caggagcatc gtgccctgag gtcggacacc 120 aaactccccatatcgactcg ctgcaagggt aaaggagcat catgtcataa gactatgtat 180 gactgctgcagcggttcctg caccagaggt agatgtggct gatccagcgc ctgatcttcc 240 cccttctgtgctctatcctt ttctgcctga gtcatcatac ctgtgctcga gcgttactag 300 tggatccgagctcggtacca agcttggcgt aatcataaaa nc 342 313 71 PRT Conus stercusmuscarum313 Met Lys Leu Thr Cys Val Val Ile Val Ala Val Leu Leu Leu Thr Ala 1 510 15 Cys Gln Leu Ile Thr Ala Asp Asp Ser Arg Gly Thr Gln Glu His Arg 2025 30 Ala Leu Arg Ser Asp Thr Lys Leu Pro Ile Ser Thr Arg Cys Lys Gly 3540 45 Lys Gly Ala Ser Cys His Lys Thr Met Tyr Asp Cys Cys Ser Gly Ser 5055 60 Cys Thr Arg Gly Arg Cys Gly 65 70 314 25 PRT Conus stercusmuscarumPEPTIDE (1)..(25) Xaa at residue 13 is Tyr, 125I-Tyr, mono-iodo- Tyr,di-iodo-Tyr, O-sulpho-Tyr or O-phospho-Tyr 314 Cys Lys Gly Lys Gly AlaSer Cys His Lys Thr Met Xaa Asp Cys Cys 1 5 10 15 Ser Gly Ser Cys ThrArg Gly Arg Cys 20 25 315 33 PRT Conus arenatus 315 Gln Cys Ser Ala AsnGly Gly Ser Cys Thr Arg His Phe His Cys Cys 1 5 10 15 Ser Leu Tyr CysAsn Lys Asp Ser Ser Val Cys Val Ala Thr Ser Tyr 20 25 30 Pro 316 28 PRTConus arenatus 316 Thr Cys Asn Thr Pro Thr Glu Tyr Cys Thr Leu His ArgHis Cys Cys 1 5 10 15 Ser Gly Tyr Cys His Lys Thr Ile Gln Ala Cys Ser 2025 317 33 PRT Conus arenatus 317 Gln Cys Thr Pro Asn Gly Gly Ser Cys SerArg His Phe His Cys Cys 1 5 10 15 Ser Leu Tyr Cys Asn Lys Ser Thr GlyVal Cys Ile Ala Thr Ser Tyr 20 25 30 Pro 318 33 PRT Conus arenatus 318Gln Cys Thr Pro Asn Gly Gly Ser Cys Ser Arg His Phe His Cys Cys 1 5 1015 Ser Leu Tyr Cys Asn Lys Ser Thr Gly Val Cys Ile Ala Thr Ser Tyr 20 2530 Pro 319 27 PRT Conus arenatus 319 Glu Cys Thr Pro Pro Gly Gly Ala CysGly Leu Pro Thr His Cys Cys 1 5 10 15 Gly Phe Cys Asp Thr Ala Asn AsnArg Cys Leu 20 25 320 28 PRT Conus arenatus 320 Thr Cys Asn Thr Pro ThrGlu Tyr Cys Thr Leu His Gln His Cys Cys 1 5 10 15 Ser Gly His Cys HisLys Thr Ile Gln Ala Cys Ala 20 25 321 30 PRT Conus arenatus 321 Gln CysSer Pro Ile Gly Gly Tyr Cys Thr Leu His Ile His Cys Cys 1 5 10 15 SerAsn His Cys Ile Lys Pro Ile Gly Arg Cys Val Ala Thr 20 25 30 322 30 PRTConus arenatus 322 Gln Cys Leu Pro Asn Gly Gly Tyr Cys Thr Leu His IleHis Cys Cys 1 5 10 15 Ser Asp His Cys Ile Lys Pro Ile Asp Arg Cys ValAla Thr 20 25 30 323 25 PRT Conus aurisiacus 323 Cys Lys Gly Lys Gly LysPro Cys Ser Arg Ile Ser Tyr Asn Cys Cys 1 5 10 15 Thr Gly Ser Cys ArgSer Gly Lys Cys 20 25 324 32 PRT Conus aurisiacus 324 Cys Met Glu AlaGly Ser Tyr Cys Gly Ser Thr Thr Arg Ile Cys Cys 1 5 10 15 Gly Phe CysAla Tyr Phe Gly Lys Lys Cys Ile Asp Tyr Pro Ser Asn 20 25 30 325 25 PRTConus aurisiacus 325 Cys Lys Ala Lys Gly Lys Pro Cys Ser Arg Ile Ala TyrAsn Cys Cys 1 5 10 15 Thr Gly Ser Cys Arg Ser Gly Lys Cys 20 25 326 26PRT Conus aurisiacus 326 Cys Ala Ser Tyr Gly Lys Pro Cys Gly Ile Asp AsnAsp Cys Cys Asn 1 5 10 15 Ala Cys Asp Pro Gly Arg Asn Ile Cys Thr 20 25327 36 PRT Conus bullatus 327 Ser Thr Ser Cys Met Glu Ala Gly Ser TyrCys Gly Pro Ala Thr Thr 1 5 10 15 Lys Ile Cys Cys Asp Phe Cys Ser ProPhe Ser Asp Arg Cys Met Asn 20 25 30 Asn Pro Asn Asn 35 328 31 PRT Conusbullatus 328 Cys Ile Thr Pro Gly Thr Arg Cys Lys Val Pro Ser Gln Cys CysArg 1 5 10 15 Gly Pro Cys Lys Asn Gly Arg Cys Thr Pro Ser Pro Ser GluTrp 20 25 30 329 26 PRT Conus bullatus 329 Cys Ala Thr Tyr Gly Lys ProCys Gly Ile Gln Asn Asp Cys Cys Asn 1 5 10 15 Thr Cys Asp Pro Ala ArgArg Thr Cys Thr 20 25 330 25 PRT Conus bullatus 330 Cys Lys Gly Pro GlyAla Ser Cys Ile Arg Ile Ala Tyr Asn Cys Cys 1 5 10 15 Lys Tyr Ser CysArg Asn Gly Lys Cys 20 25 331 36 PRT Conus bullatus 331 Ser Thr Ser CysMet Ala Ala Gly Ser Tyr Cys Gly Pro Ala Thr Thr 1 5 10 15 Asn Ile CysCys Asp Phe Cys Ser Pro Phe Ser Asp Arg Cys Met Lys 20 25 30 Lys Pro AsnAsn 35 332 25 PRT Conus bullatus 332 Cys Lys Ser Lys Gly Ser Ser Cys HisArg Thr Ser Tyr Asp Cys Cys 1 5 10 15 Thr Gly Ser Cys Arg Asn Gly ArgCys 20 25 333 25 PRT Conus catus 333 Cys Lys Ser Thr Gly Ala Ser Cys ArgArg Thr Ser Tyr Asp Cys Cys 1 5 10 15 Thr Gly Ser Cys Arg Ser Gly ArgCys 20 25 334 25 PRT Conus catus 334 Cys Gln Gly Arg Gly Ala Ser Cys ArgLys Thr Met Tyr Asn Cys Cys 1 5 10 15 Ser Gly Ser Cys Asn Arg Gly SerCys 20 25 335 28 PRT Conus catus 335 Cys Leu Pro Ala Gly Glu Ser Cys LeuPhe Ser Arg Ile Arg Cys Cys 1 5 10 15 Gly Thr Cys Ser Ser Val Leu LysSer Cys Val Ser 20 25 336 25 PRT Conus catus 336 Cys Gln Gly Arg Gly GlyPro Cys Thr Lys Ala Val Phe Asn Cys Cys 1 5 10 15 Ser Gly Ser Cys AsnArg Gly Arg Cys 20 25 337 26 PRT Conus catus 337 Cys Ala Thr Tyr Gly LysPro Cys Gly Ile Gln Asn Asp Cys Cys Asn 1 5 10 15 Thr Cys Asp Pro AlaArg Lys Thr Cys Thr 20 25 338 25 PRT Conus catus 338 Cys Arg Gly Arg GlyGly Pro Cys Thr Lys Ala Met Phe Asn Cys Cys 1 5 10 15 Ser Gly Ser CysAsn Arg Gly Arg Cys 20 25 339 33 PRT Conus caracteristicus 339 Gln CysSer Ala Asn Gly Gly Ser Cys Thr Arg His Phe His Cys Cys 1 5 10 15 SerLeu Tyr Cys Asn Lys Asp Ser Ser Val Cys Val Ala Thr Ser Tyr 20 25 30 Pro340 26 PRT Conus consors 340 Cys Ala Ser Tyr Gly Lys Pro Cys Gly Ile AspAsn Asp Cys Cys Asn 1 5 10 15 Thr Cys Asp Pro Ala Arg Lys Thr Cys Thr 2025 341 25 PRT Conus consors 341 Cys Lys Gly Thr Gly Lys Pro Cys Ser ArgIle Ala Tyr Asn Cys Cys 1 5 10 15 Thr Gly Ser Cys Arg Ser Gly Lys Cys 2025 342 36 PRT Conus consors 342 Ala Thr Asp Cys Ile Glu Ala Gly Asn TyrCys Gly Pro Thr Val Met 1 5 10 15 Lys Ile Cys Cys Gly Phe Cys Ser ProTyr Ser Lys Ile Cys Met Asn 20 25 30 Tyr Pro Gln Asn 35 343 27 PRT Conuscatus 343 Cys Lys Gly Lys Gly Ala Ser Cys Thr Arg Leu Met Tyr Asp CysCys 1 5 10 15 His Gly Ser Cys Ser Ser Ser Lys Gly Arg Cys 20 25 344 25PRT Conus consors 344 Cys Lys Gly Lys Gly Ala Ser Cys His Arg Thr SerTyr Asp Cys Cys 1 5 10 15 Thr Gly Ser Cys Asn Arg Gly Lys Cys 20 25 34526 PRT Conus consors 345 Cys Ala Ser Tyr Gly Lys Pro Cys Gly Ile Tyr AsnAsp Cys Cys Asn 1 5 10 15 Thr Cys Asp Pro Ala Arg Lys Thr Cys Thr 20 25346 25 PRT Conus consors 346 Cys Lys Gly Thr Gly Lys Pro Cys Ser Arg ValAla Tyr Asn Cys Cys 1 5 10 15 Thr Gly Ser Cys Arg Ser Gly Lys Cys 20 25347 35 PRT Conus consors 347 Ser Thr Ser Cys Met Lys Ala Gly Ser Tyr CysArg Ser Thr Thr Arg 1 5 10 15 Thr Cys Cys Gly Tyr Cys Ala Tyr Phe GlyLys Phe Cys Ile Asp Phe 20 25 30 Pro Ser Asn 35 348 25 PRT Conuscircumcisus 348 Cys Lys Gly Lys Gly Ala Ser Cys Arg Lys Thr Met Tyr AsnCys Cys 1 5 10 15 Ser Gly Ser Cys Ser Asn Gly Arg Cys 20 25 349 35 PRTConus circumcisus 349 Ser Thr Ser Cys Met Glu Ala Gly Ser Tyr Cys ArgSer Thr Thr Arg 1 5 10 15 Thr Cys Cys Gly Tyr Cys Ser Tyr Phe Ser LysLys Cys Ile Asp Phe 20 25 30 Pro Ser Asn 35 350 27 PRT Conus circumcisus350 Cys Lys Ser Lys Gly Ala Lys Cys Ser Arg Leu Met Tyr Asp Cys Cys 1 510 15 Ser Gly Ser Cys Ser Arg Tyr Ser Gly Arg Cys 20 25 351 35 PRT Conuscircumcisus 351 Ser Thr Gly Cys Met Lys Ala Gly Ser Tyr Cys Arg Ser ThrThr Arg 1 5 10 15 Thr Cys Cys Gly Tyr Cys Ala Tyr Phe Gly Lys Lys CysIle Asp Tyr 20 25 30 Pro Ser Asn 35 352 28 PRT Conus dalli 352 Ser CysThr Pro Pro Gly Gly Pro Cys Gly Tyr Tyr Asn Asp Cys Cys 1 5 10 15 SerHis Gln Cys Asn Ile Ser Arg Asn Lys Cys Glu 20 25 353 25 PRT Conusdistans PEPTIDE (1)..(25) Xaa is Hyp 353 Cys Glu Asp Xaa Gly Glu Xaa CysGly Ser Asp His Ser Cys Cys Gly 1 5 10 15 Gly Ser Cys Asn His Asn ValCys Ala 20 25 354 27 PRT Conus ermineus 354 Pro Cys Lys Pro Lys Gly ArgLys Cys Phe Pro His Gln Lys Asp Cys 1 5 10 15 Cys Asn Lys Thr Cys ThrArg Ser Lys Cys Pro 20 25 355 27 PRT Conus ermineus 355 Ala Cys Trp SerSer Gly Thr Pro Cys Gly Thr Asp Ser Leu Cys Cys 1 5 10 15 Gly Gly CysAsn Val Ser Lys Ser Lys Cys Asn 20 25 356 27 PRT Conus geographus 356Cys Lys Ser Pro Gly Ser Ser Cys Ser Pro Thr Ser Tyr Asn Cys Cys 1 5 1015 Arg Ser Cys Asn Pro Tyr Ala Lys Arg Cys Tyr 20 25 357 29 PRT Conusgeographus 357 Cys Lys Ser Pro Gly Thr Pro Cys Ser Arg Gly Met Arg AspCys Cys 1 5 10 15 Thr Pro Cys Leu Leu Tyr Ser Asn Lys Cys Arg Arg Tyr 2025 358 30 PRT Unknown unknown Conus species 358 Cys Leu Ser Pro Gly SerArg Cys His Lys Thr Met Arg Asn Cys Cys 1 5 10 15 Thr Ser Cys Ser SerTyr Lys Gly Lys Cys Arg Pro Arg Lys 20 25 30 359 27 PRT Unknown unknownConus species 359 Cys Lys Pro Pro Gly Arg Lys Cys Leu Asn Arg Lys AsnGlu Cys Cys 1 5 10 15 Ser Lys Phe Cys Asn Glu His Leu His Met Cys 20 25360 26 PRT Unknown unknown Conus species 360 Cys Lys Pro Pro Arg Arg LysCys Leu Lys Ile Lys Asp Lys Cys Cys 1 5 10 15 Asn Phe Cys Asn Thr HisLeu Asn Met Cys 20 25 361 28 PRT Unknown unknown Conus species 361 CysAla Gly Pro Gly Thr Ile Cys Pro Asn Arg Val Cys Cys Gly Tyr 1 5 10 15Cys Ser Lys Arg Thr His Leu Cys His Ser Arg Thr 20 25 362 27 PRT Conuslaterculatus 362 Lys Cys Trp Pro Ser Gly Ser Tyr Cys Arg Ala Asn Ser LysCys Cys 1 5 10 15 Ser Gly Cys Asp Arg Asn Arg Asn Lys Cys Tyr 20 25 36327 PRT Conus laterculatus 363 Cys Leu Pro Pro Gly Ser Tyr Cys Lys AlaThr Thr Glu Val Cys Cys 1 5 10 15 Ser Ser Cys Leu Gln Phe Ala Gln IleCys Ser 20 25 364 30 PRT Conus lynceus 364 Cys Lys Ser Pro Gly Ser ProCys Ser Val Thr Ser Tyr Asn Cys Cys 1 5 10 15 Thr Phe Cys Ser Ser TyrThr Lys Lys Cys Arg Ala Ser Leu 20 25 30 365 28 PRT Conus lynceus 365Cys Ala Gly Pro Gly Ala Ile Cys Pro Asn Arg Val Cys Cys Gly Tyr 1 5 1015 Cys Ser Lys Arg Thr His Leu Cys His Ser Arg Thr 20 25 366 27 PRTConus lynceus 366 Ala Cys Trp Ser Ser Gly Thr Pro Cys Gly Thr Asp SerLeu Cys Cys 1 5 10 15 Gly Gly Cys Asn Val Ser Lys Ser Lys Cys Asn 20 25367 27 PRT Conus lynceus 367 Lys Cys Trp Ser Pro Gly Thr Tyr Cys Arg AlaHis Ser Lys Cys Cys 1 5 10 15 Arg Gly Cys Asp Gln Asn Arg Asn Lys CysTyr 20 25 368 29 PRT Conus laterculatus 368 Cys Lys Ser Pro Gly Ser SerCys Ser Val Ser Met Arg Asn Cys Cys 1 5 10 15 Thr Ser Cys Asn Ser ArgThr Lys Lys Cys Thr Arg Arg 20 25 369 27 PRT Conus laterculatus 369 ThrCys Trp Pro Ser Gly Thr Ala Cys Gly Ile Asp Ser Asn Cys Cys 1 5 10 15Ser Gly Cys Asn Val Ser Arg Ser Lys Cys Asn 20 25 370 27 PRT Conuslaterculatus 370 Lys Cys Trp Pro Ser Gly Ser Tyr Cys Arg Ala Asn Ser LysCys Cys 1 5 10 15 Ser Gly Cys Asp Arg Asn Arg Ser Lys Cys Asn 20 25 37137 PRT Conus leopardus 371 Ser Leu Phe Glu Cys Ala Pro Ser Gly Gly ArgCys Gly Phe Leu Lys 1 5 10 15 Ser Cys Cys Glu Gly Tyr Cys Asp Gly GluSer Thr Ser Cys Val Ser 20 25 30 Gly Pro Tyr Ser Ile 35 372 30 PRT Conusleopardus 372 Trp Pro Leu Asp Cys Thr Ala Pro Ser Gln Pro Cys Gly TyrPhe Pro 1 5 10 15 Arg Cys Cys Gly His Cys Asp Val Arg Arg Val Cys ThrSer 20 25 30 373 31 PRT Conus leopardus 373 Cys Met Ser Pro Gly Gly IleCys Gly Asp Phe Gly Asp Cys Cys Glu 1 5 10 15 Ile Cys Asn Val Tyr GlyIle Cys Val Ser Asp Leu Pro Gly Ile 20 25 30 374 27 PRT Conus leopardus374 Tyr Cys Ala Pro Pro Gly Gly Ala Cys Gly Phe Phe Asp His Cys Cys 1 510 15 Gly Tyr Cys Glu Thr Phe Tyr Asn Thr Cys Arg 20 25 375 25 PRT Conusmagus 375 Cys Lys Gly Thr Gly Lys Pro Cys Ser Arg Ile Ala Tyr Asn CysCys 1 5 10 15 Thr Gly Ser Cys Arg Ser Gly Lys Cys 20 25 376 26 PRT Conusmagus 376 Cys Ala Ser Tyr Gly Lys Pro Cys Gly Ile Tyr Asn Asp Cys CysAsn 1 5 10 15 Thr Cys Asp Pro Ala Arg Lys Thr Cys Thr 20 25 377 27 PRTConus miles 377 Cys Asn Asp Arg Gly Gly Gly Cys Ser Gln His Pro His CysCys Gly 1 5 10 15 Gly Thr Cys Asn Lys Leu Ile Gly Val Cys Leu 20 25 37825 PRT Conus monachus 378 Cys Lys Ser Thr Gly Lys Ser Cys Ser Arg IleAla Tyr Asn Cys Cys 1 5 10 15 Thr Gly Ser Cys Arg Ser Gly Lys Cys 20 25379 25 PRT Conus monachus 379 Cys Lys Gly Lys Gly Ser Ser Cys Ser ArgThr Met Tyr Asn Cys Cys 1 5 10 15 Thr Gly Ser Cys Asn Arg Gly Lys Cys 2025 380 35 PRT Conus obscurus 380 Ser Pro Pro Cys Met Lys Gly Gly Ser SerCys Arg Gly Thr Thr Gly 1 5 10 15 Val Cys Cys Gly Phe Cys Ser Asp PheGly Tyr Lys Cys Arg Asp Tyr 20 25 30 Pro Gln Asn 35 381 28 PRT Conusobscurus 381 Cys Leu Pro Asp Gly Thr Ser Cys Leu Phe Ser Arg Ile Arg CysCys 1 5 10 15 Gly Thr Cys Ser Ser Ile Leu Lys Ser Cys Val Ser 20 25 38227 PRT Conus purpurascens PEPTIDE (1)..(27) Xaa is Hyp 382 Xaa Cys LysThr Xaa Gly Arg Lys Cys Phe Xaa His Gln Lys Asp Cys 1 5 10 15 Cys GlyArg Ala Cys Ile Ile Thr Ile Cys Pro 20 25 383 26 PRT Conus purpurascensPEPTIDE (1)..(26) Xaa at residue 5 is Hyp; Xaa at residue 12 isgamma-carboxy-Glu 383 Ser Cys Lys Leu Xaa Gly Ala Tyr Cys Asn Ala XaaAsp Tyr Asp Cys 1 5 10 15 Cys Leu Arg Cys Lys Val Gly Gly Thr Cys 20 25384 27 PRT Conus purpurascens 384 Pro Cys Lys Lys Thr Gly Arg Lys CysPhe Pro His Gln Lys Asp Cys 1 5 10 15 Cys Gly Arg Ala Cys Ile Ile ThrIle Cys Pro 20 25 385 30 PRT Conus pulicarius 385 Gln Cys Ser Pro AsnGly Gly Ser Cys Ser Arg His Phe His Cys Cys 1 5 10 15 Ser Leu Tyr CysAsn Lys Asn Thr Gly Val Cys Ile Ala Thr 20 25 30 386 27 PRT Conuspulicarius 386 Glu Cys Thr Pro Pro Asp Gly Ala Cys Gly Leu Pro Thr HisCys Cys 1 5 10 15 Gly Phe Cys Asp Met Ala Asn Asn Arg Cys Leu 20 25 38727 PRT Conus pulicarius 387 Glu Cys Thr Pro Pro Gly Gly Ala Cys Gly LeuPro Thr His Cys Cys 1 5 10 15 Gly Phe Cys Asp Met Ala Asn Asn Arg CysLeu 20 25 388 28 PRT Conus radiatus 388 His Gly Cys Lys Pro Leu Lys ArgArg Cys Phe Asn Asp Lys Glu Cys 1 5 10 15 Cys Ser Lys Phe Cys Asn SerVal Arg Lys Gln Cys 20 25 389 28 PRT Conus radiatus 389 Arg Gly Cys LysPro Leu Lys Arg Arg Cys Phe Asn Asp Lys Glu Cys 1 5 10 15 Cys Ser LysPhe Cys Asn Ser Val Arg Asn Gln Cys 20 25 390 27 PRT Conus rattus 390Cys Asn Ala Arg Asn Asp Gly Cys Ser Gln His Ser Gln Cys Cys Ser 1 5 1015 Gly Ser Cys Asn Lys Thr Ala Gly Val Cys Leu 20 25 391 27 PRT Conusrattus 391 Cys Asn Ala Arg Asn Ser Gly Cys Ser Gln His Pro Gln Cys CysSer 1 5 10 15 Gly Ser Cys Asn Lys Thr Ala Gly Val Cys Leu 20 25 392 27PRT Conus rattus 392 Cys Asn Ala Arg Asn Ser Gly Cys Ser Gln His Pro GlnCys Cys Ser 1 5 10 15 Gly Ser Cys Asn Lys Thr Leu Gly Val Cys Leu 20 25393 34 PRT Conus rattus 393 Ala Cys Thr Pro Glu Gly Gly Ala Cys Ser SerGly Arg His Cys Cys 1 5 10 15 Gly Phe Cys Asp Asn Val Ser His Thr CysTyr Gly Glu Thr Pro Ser 20 25 30 Leu His 394 36 PRT Conus striatus 394Ala Thr Asp Cys Ile Glu Ala Gly Asn Tyr Cys Gly Pro Thr Val Met 1 5 1015 Lys Ile Cys Cys Gly Phe Cys Ser Pro Tyr Ser Lys Ile Cys Met Asn 20 2530 Tyr Pro Lys Asn 35 395 26 PRT Conus striatus 395 Cys Lys Leu Lys GlyGln Ser Cys Arg Arg Thr Met Tyr Asp Cys Cys 1 5 10 15 Ser Gly Ser CysGly Arg Arg Gly Lys Cys 20 25 396 25 PRT Conus striatus 396 Cys Lys AlaAla Gly Lys Ser Cys Ser Arg Ile Ala Tyr Asn Cys Cys 1 5 10 15 Thr GlySer Cys Arg Ser Gly Lys Cys 20 25 397 26 PRT Conus striatus 397 Cys GluSer Tyr Gly Lys Pro Cys Gly Ile Tyr Asn Asp Cys Cys Asn 1 5 10 15 AlaCys Asp Pro Ala Lys Lys Thr Cys Thr 20 25 398 27 PRT Conusstercusmuscarum 398 Cys Lys Ser Lys Gly Ala Lys Cys Ser Arg Leu Met TyrAsp Cys Cys 1 5 10 15 Ser Gly Ser Cys Ser Gly Tyr Thr Gly Arg Cys 20 25399 35 PRT Conus stercusmuscarum 399 Thr Thr Ser Cys Met Gln Ala Gly SerTyr Cys Gly Ser Thr Thr Arg 1 5 10 15 Ile Cys Cys Gly Tyr Cys Ala TyrPhe Gly Lys Lys Cys Ile Asp Tyr 20 25 30 Pro Ser Asn 35 400 26 PRT Conusstercusmuscarum 400 Cys Ala Ser Tyr Gly Lys Pro Cys Gly Ile Asp Asn AspCys Cys Asn 1 5 10 15 Ala Cys Asp Pro Ala Arg Asn Ile Cys Thr 20 25 40126 PRT Conus stercusmuscarum 401 Cys Val Ser Tyr Gly Lys Pro Cys Gly IleAsp Asn Asp Cys Cys Asn 1 5 10 15 Ala Cys Asp Pro Ala Arg Asn Ile CysThr 20 25 402 25 PRT Conus stercusmuscarum 402 Cys Lys Gly Lys Gly AlaSer Cys His Lys Thr Met Tyr Asp Cys Cys 1 5 10 15 Ser Gly Ser Cys ThrArg Gly Arg Cys 20 25 403 25 PRT Conus striolatus 403 Cys Lys Gly LysGly Ala Ser Cys Leu Arg Thr Ala Tyr Asp Cys Cys 1 5 10 15 Thr Gly SerCys Asn Arg Gly Arg Cys 20 25 404 24 PRT Conus striolatus 404 Cys ArgPro Ser Gly Ser Asn Cys Gly Asn Ile Ser Ile Cys Cys Gly 1 5 10 15 ArgCys Val Asn Arg Arg Cys Thr 20 405 35 PRT Conus striolatus 405 Ser ThrSer Cys Met Lys Ala Gly Ser Tyr Cys Val Ala Thr Thr Arg 1 5 10 15 IleCys Cys Gly Tyr Cys Ala Tyr Phe Gly Lys Ile Cys Ile Asp Tyr 20 25 30 ProLys Asn 35 406 28 PRT Conus textile 406 Tyr Cys Thr Pro His Gly Gly HisCys Gly Tyr His Asn Asp Cys Cys 1 5 10 15 Ser His Gln Cys Asn Ile AsnArg Asn Lys Cys Glu 20 25 407 31 PRT Conus viola 407 Cys Ile Thr Leu GlyThr Arg Cys Lys Val Pro Ser Gln Cys Cys Arg 1 5 10 15 Ser Ser Cys LysAsn Gly Arg Cys Ala Pro Ser Pro Glu Glu Trp 20 25 30 408 25 PRT Conusviola 408 Cys Lys Ser Arg Gly Ser Ser Cys Arg Arg Thr Ser Tyr Asp CysCys 1 5 10 15 Thr Gly Ser Cys Arg Asn Gly Lys Cys 20 25 409 36 PRT Conusviola 409 Ser Thr Ser Cys Met Glu Ala Arg Ser Tyr Cys Gly Pro Ala ThrThr 1 5 10 15 Lys Ile Cys Cys Asp Phe Cys Ser Pro Phe Ser Asp Arg CysMet Asn 20 25 30 Asn Pro Asn Asn 35 410 25 PRT Conus viola 410 Cys LysGly Pro Gly Ala Ile Cys Ile Arg Ile Ala Tyr Asn Cys Cys 1 5 10 15 LysTyr Ser Cys Gly Asn Gly Lys Cys 20 25 411 28 PRT Conus viola 411 Tyr CysThr Pro Tyr Gly Gly His Cys Gly Tyr Tyr Asn Asp Cys Cys 1 5 10 15 SerHis Gln Cys Asn Ile Asn Arg Asn Lys Cys Glu 20 25 412 27 PRT Conustextile 412 Cys Thr Pro Tyr Gly Gly His Cys Gly Tyr Asn His Asp Cys CysSer 1 5 10 15 His Gln Cys Asn Ile Asn Arg Asn Lys Cys Glu 20 25 413 26PRT Conus tulipa PEPTIDE (1)..(26) Xaa is Hyp 413 Cys Lys Ser Trp GlySer Xaa Cys Ser Xaa Thr Ser Thr Asn Cys Cys 1 5 10 15 Trp Ser Cys SerPro Tyr Arg Lys Lys Cys 20 25

What is claimed is:
 1. An isolated peptide selected from the groupconsisiting of: (a) a peptide set forth in Table 2 (b) a derivative ofthe peptide in (a); and (c) a propeptide set forth in Table 1 .
 2. Theisolated peptide of claim 1, wherein Xaa₁ is Lys, Xaa2 is Tyr, Xaa3 isGlu and Xaa₅ is Trp.
 3. An isolated nucleic acid encoding anω-conopeptide propeptide having an amino acid sequence set forth inTable
 1. 4. The isolated nucleic acid of claim 3, wherein the nucleicacid comprises a nucleotide sequence set forth in Table
 1. 5. Anisolated conopeptide propeptide having an amino acid sequence set forthin Table
 1. 6. A method for treating or preventing disorders associatedwith voltage gated ion channel disorders in which comprisesadministering to a patient in need thereof a therapeutically effectiveamount of an active agent selected from the group consisting of peptides(a) and (b) of claim 1 or a pharmaceutically acceptible salt thereof. 7.The method of claim 6, wherein said disorder is a neurologic disorder.8. The method of claim 7, wherein said neurologic disorder is a seizure.9. The method of claim 8, wherein said seizure is seizure is associatedwith epilepsy.
 10. The method of claim 7, wherein said neurologicdisorder is a neurotoxic injury associated with conditions of hypoxia,anoxia or ischemia.
 11. The method of claim 10, wherein said neurotoxicinjury is associated with stroke, cerebrovascular accident, brain orspinal cord trauma, myocardial infarct, physical trauma, drownings,suffocation, perinatal asphyxia, or hypoglycemic events.
 12. The methodof claim 6, wherein said disorder is pain.
 13. The method of claim 12,wherein said pain is migraine, acute pain, persistent pain, neuropathicpain or nociceptive pain.
 14. The method of claim 6, wherein saiddisorder is inflammation.
 15. The method of claim 6, wherein saiddisorder is a cardiovascular disorder.